InnateDB Innate Immunity Genes

Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also established a project to annotate genes that have a role in the innate immune response. This has been initiated in response to the fact that Gene Ontology annotation of the innate immune response is quite limited in the numbers of genes which have been identified and in response to the fact that many users have been eager to have a defined list of innate immune genes. For innate immune gene annotation, curators employ a new tool in the InnateDB curation system to associate relevant genes with publications which provide evidence for that gene having a role in innate immunity. Along with the link to the relevant publication(s), the curators provide a one-line summary of the role similar to Entrez GeneRIFs. Such genes are also automatically associated with the Gene Ontology term "innate immune response" in InnateDB, which provides a more comprehensive list of these genes for use in the InnateDB Gene Ontology over-representation analysis tool. To date, 1693 genes have been annotated to some extent (as this is an on-going process). It should be noted that it is not the intention of InnateDB to comprehensively annotate all the roles of a given gene, but rather to provide a brief indication if a gene has a role in innate immunity. You can download all InnateDB curated genes with their annotations as Excel sheet.

This list provides details of the 2308 genes which have been annotated by either InnateDB or Gene Ontology as having a role in the innate immune response and is updated weekly.

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Gene name Annotation Added
IKBKB (Homo sapiens) PubMed 18692471: IKBKB regulates late-phase allergic reactions promoted by the release of pro-inflammatory cytokines in an NF-kappaB-dependent manner.
PubMed 20627395: Phosphorylated IKBKB is conjugated with a monoubiquitin by the E3 ubiquitin ligase TRIM21 leading to down-regulatioin of IKBKB-induced NF-kappaB signalling. The TRIM21-mediated monoubiquitination is involved in the translocation of active IKBKB to autophagosomes.
PubMed 21138416: IKBKB and other IKK kinases regulate each other by an intricate network involving phosphorylation of their catalytic and regulatory (NEMO, TANK) subunits to balance their activities during innate immunity.
PubMed 24323043: GNB2L1 (RACK1) negatively regulates NFκB activation by interacting with CHUK and IKBKB. The interaction interferes with the recruitment of the IKK complex to TRAF2 .
PubMed 26620909: The reversible ubiquitin editing of NLRC5 determines NLRC5?? IKBKB interaction dynamics and plays a crucial role in precisely regulating NFκB signalling
PubMed 26394554: Enterovirus 71 2C protein binds to RELA and IKBKB to inhibit NF-kB activation and evade innate immune defenses.
2017-05-29
TRAF6 (Homo sapiens) PubMed 16184196: TRAF6 is an adapter protein linking kinases to TNF receptor, and IL-1 receptor signalling pathways, and also has E3 ubiquitin ligase activity.
PubMed 18617513: TRAF6 autoubiquitination and its interaction with Ubc13 are dependent on zinc finger 1 (ZF1) motif and an intact RING domain, necessary elements in signalling by IL-1, LPS and RANKL.
PubMed 18922473: TRAF6 is specifically required for the Smad-independent activation of JNK and p38, and its carboxyl TRAF homology domain physically interacts with TGF-beta receptors that activate JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway.
PubMed 18984593: TRAF6 and MEK kinase 1 (MEKK1) play a pivotal role in the retinoic-acid-inducible gene-I (RIG-I)-like helicase antiviral pathway, where TRAF6 and MEKK1 activate NF-kappaB and mitogen-activated protein kinases via MAVS and this is critical for the optimal induction of type I interferons.
PubMed 19091594: TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation through its ubiquitin ligase activity.
PubMed 12140561: TRAF6 regulates several signalling cascades in innate immunity, adaptive immunity and bone homeostasis.
PubMed 20449947: TRAF6 competes with TRAF2 for CD40 binding to regulate NF-kappaB activation in human B lymphocytes, thereby limiting the capacity of CD40 engagement to induce NF-kappaB activation.
PubMed 20512936: TRAF6 is autoinhibited by an intramolecular interaction which is counteracted by trans-ubiquitination and TRAF auto-ubiquitination is a means of sustaining an open conformation active in downstream signalling.
PubMed 20622119: TRAF6 interacts with CSF2RB to mediate NF-kappaB signalling, demonstrating a novel TRAF6-dependent signalling pathway association with a type I cytokine receptor.
PubMed 21185369: TRAF6 is a E3 ubiquitin ligase that activates NFKB pathway in response to innate and adaptive immunity stimuli. TRAF6 protein contains a highly conserved TRAF-C domain that contributes to oligomerization and its interaction to upstream signalling molecules and a RING domain dimerization interface that is functionally important for ubiquitination and the activation of NFKB.
PubMed 21220427: TRAF6 is polyubiquitinated and disassembled during endotoxin tolerization; a process which impairs the production of LPS-induced pro-inflammatory cytokines without inhibition expression of anti-inflammatory or anti-microbial mediators.
PubMed 22033459: TRAF6 is degraded in the proteasome upon TLR stimulation in macrophages. (Demonstrated in mice)
PubMed 24670424: Following NOD2 activation, IRF4 interacts with MYD88, TRAF6, and RIPK2 and downregulates K63-linked polyubiquitinylation of RICK and TRAF6 leading to disruption of NFkB activation pathways.
PubMed 24670381: MIR146A is a potent negative regulator of the innate immune response in keratinocytes through downregulation of the IRAK1/TRAF6/NFκB pathway.
PubMed 25027037: STAT1 is directly recruited to TRAF6, demonstrating cross-talk between the TLR and JAK/STAT signalling pathways, and this direct activation of STAT1 by TLR signalling suggests a crucial role for STAT1 in TLR-induced inflammation. Demonstrated in mice.
PubMed 25371197: ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
PubMed 26221041: Reversible arginine methylation of TRAF6 is regulated by PRMT1 and JMJD6 and this in turn regulates TRAF6-dependent TLR signalling.
PubMed 26385923: MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2.
2017-05-29
MAVS (Homo sapiens) PubMed 19036819: MAVS oligomer is essential in the formation of a multiprotein membrane-associated signalling complex that enables downstream activation of IRF3 and NF-kappaB in antiviral innate immunity.
PubMed 16177806: MAVS is a caspase recruitment domain (CARD)-containing adaptor protein that interacts with DDX58 (RIG-I) and recruits CHUK (IKKalpha), IKBKB (IKKbeta) and IKBKE (IKKepsilon) kinases by means of its C-terminal region, leading to the activation of NF-kappaB and IRF3.
PubMed 16125763: MAVS is an adaptor protein that contains an N-terminal caspase recruitment domain (CARD)-like domain and a C-terminal transmembrane domain, both of which are essential for MAVS signalling, while the transmembrane domain also targets MAVS to the mitochondria.
PubMed 20032188: MAVS facilitates cell death by disrupting the mitochondrial membrane potential and by activating caspases.
PubMed 20140199: MAVS-dependent RIG-I-like receptor (RLR) signalling regulates the quantity, quality, and balance of the immune response to West Nile virus (WNV) infection.
PubMed 20451243: MAVS in peroxisomes induces a rapid interferon-independent expression of defence factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signalling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response.
PubMed 20554965: MAVS interacts with hepatitis B virus X protein and this promotes the degradation of MAVS via Lys(136) ubiquitination, preventing the induction of IFN-beta.
PubMed 20661427: MAVS (IPS-1) interacts with MFN1 upon virus-infection or 5'ppp-RNA activation through redistribution of MAVS to form speck-like aggregates in cells.
PubMed 20699220: MAVS (IPS1) plays an important role in regulating the host anti-viral response by binding to viral polymerase and inhibiting IFN-beta production.
PubMed 21110072: MAVS negatively regulates the stability of voltage-dependent anion channel 1 (VDAC1) and thereby inhibits apoptosis in the response to release of cytochrome c.
PubMed 21454965: The MAVS signalling pathway in non-myeloid cells is crucial for dsRNA-mediated natural killer cell activation. (Demonstrated in murine model)
PubMed 22844514: Tyrosine phosphorylation of MAVS at amino acid residue Tyr9 is critical for the induction of IFNB signalling.
PubMed 23028806: MAVS mRNA is degraded in response to foreign RNA and poly(I:C) to suppress hyper-immune reaction in late-phase antiviral signalling.
PubMed 23582325: MAVS is required for optimal NLRP3 inflammasome activity by mediating mitochondrial recruitment of NLRP3.
PubMed 23555247: MAVS is targeted by enterovirus protease to evade antiviral immunity.
PubMed 23951545: The binding of MAVS to Traf2, Traf5, and Traf6 is dependent on virus infection and MAVS polymerization. The TRAF proteins promote ubiquitination that recruits IKBKG binding to the MAVS signalling complex.
PubMed 24651600: Upon viral infection, MAVS recruits MKK7 onto mitochondria, leading to the induction of apoptosis by MAP2K7 activated MAPK9
PubMed 25463536: Macrocyclic NS3-4A resistance-associated amino acid variants (RAVs) with substitutions at residue D168 of the hepatitis C virus protease result in an increased capacity of NS3-4A to cleave MAVS and suppress IFNB1 induction.
PubMed 25816776: RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.
PubMed 27213432: HACE1 plays an inhibitory role in virus-induced signalling by disrupting the MAVS-TRAF3 complex.
PubMed 26246171: MARCH5 modulates MAVS-mediated antiviral signalling, preventing excessive immune reactions.
PubMed 26385923: MAVS directly interacts with TRAF6 through its potential TRAF6-binding motif 2.
2017-05-29
IL29 (Homo sapiens) PubMed 21499846: IL29 is able to efficiently inhibit Herpes Simplex Virus Type-1 replication in neuronal cells by inducing the expression of TLR as well as activate the TLR-mediated interferon antiviral pathway.
PubMed 24041672: IFNL1 (IL29), IFNL2 and IFNL3 have different effects on Toll-like receptor-related gene expression in HepG2 cells.
PubMed 26130701: IFN-λ1 is able to augment TLR-mediated B cell activation, partially attributed to an upregulation of TLR7 expression
PubMed 26378160: Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.
2017-05-29
EFTUD2 (Homo sapiens) PubMed 25878102: EFTUD2 is a novel innate immune regulator that restricts hepatitis C virus infection through an RIG-I/MDA5-mediated, JAK-STAT-independent pathway.
PubMed 25878102: EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
2017-05-29
DDX58 (Homo sapiens) PubMed 15208624: DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling.
PubMed 18948594: DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade.
PubMed 19074283: DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
PubMed 19683681: DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well.
PubMed 18523264: DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
PubMed 19915568: DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production.
PubMed 20403326: DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity.
PubMed 20406818: DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
PubMed 20511549: DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
PubMed 19936053: DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
PubMed 21690088: DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58.
PubMed 21695051: DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58.
PubMed 22072774: DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice)
PubMed 22912779: Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
PubMed 23744645: DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
PubMed 23950712: RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
PubMed 24448099: ISG15 does not directly alter human rhinovirus replication but modulates immune signalling via the viral sensor protein DDX58 to impact production of CXCL10, which has been linked to innate immunity to viruses.
PubMed 24448099: Human rhinovirus infection of epithelial cells induces the expression and secretion of ISG15, which modulates immune responses via effects on DDX58, and by regulating CXCL10 production.
PubMed 24550253: The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
PubMed 25002588: IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
PubMed 25520509: Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
PubMed 25557055: DDX58 dually functions as an hepatitis B virus sensor activating innate signalling and as a direct antiviral factor by counteracting the viral polymerase in hepatocytes.
PubMed 26074083: DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
PubMed 25880109: Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
PubMed 27210312: Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
PubMed 26645583: MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
PubMed 26608320: A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
PubMed 26371557: ATP binding is required for DDX58 signalling on viral RNA. ATP hydrolysis provides an important function by recycling DDX58 and promoting its dissociation from non-pathogenic RNA.
PubMed 26378160: Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.
PubMed 25878102: EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
PubMed 26450567: MIR136 exhibits potent antiviral activity against H5N1 influenza A virus and acts as an immune agonist of DDX58.
2017-05-29
RELA (Homo sapiens) PubMed 11980335: RELA, NF-kappaB p65 subunit, is involved in the transcription regulation of many genes including those genes involved in apoptosis, response to stress and inflammation.
PubMed 21209118: RELA is a subunit of NFKB and is not essential for virus-stimulated IFNB expression, instead, RELA sustains autocrine IFNB signalling prior to infection. The absence of RELA causes significant delays in IFNB induction and consequently defective secondary antiviral gene expression. RELA maintains autocrine IFNB signalling in uninfected cells, facilitates inflammatory and adaptive immune responses following infection, and promotes infected cell survival during this process.
PubMed 21216972: RELA is critical for pulmonary host defence during Streptococcus pneumoniae pneumonia in alveolar macrophages. During pneumococcal pneumonia, only the earliest induction of cytokines depends on transcription regulated by RELA in myeloid cells, and this transcriptional activity contributes to effective immunity. (Demonstrated in murine model)
PubMed 21419662: RELA is required for IL17A production in T cell in response to bacterial infection. RELA deficient T cells resulted in a diminished innate immune response to E. coli infection. (Demonstrated in murine model)
PubMed 23271966: A RELA isoform, p43, lacks the transactivation domain but is still able to potentiate anti-viral innate immunity.
PubMed 23994473: During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
PubMed 25520509: Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
PubMed 26055519: Human papillomaviruses impair the acetylation of NFκB/RelA K310 in keratinocytes by augmenting the expression of interferon-related developmental regulator 1 (IFRD1) in an EGFR-dependent manner.
PubMed 26642243: Haploinsufficiency of A20 (HA20) is caused by high-penetrance loss-of-function germline mutations in TNFAIP3 with increased degradation of NFKBIA, nuclear translocation of RELA, increased expression of NFκB mediated proinflammatory cytokines, and defective deubiquitinating activity.
PubMed 26296289: MIR223 regulates macrophage function by modulating cytokine production and NF-κB activation through inhibition of RELA phosphorylation and nuclear translocation.
PubMed 26394554: Enterovirus 71 2C protein binds to RELA and IKBKB to inhibit NF-kB activation and evade innate immune defenses.
2017-05-29
IRF3 (Homo sapiens) PubMed 9463386: IRF3 is a transcription factor that activates type-1 interferon (IFN) and IFN responsive genes.
PubMed 11991981: IRF3 is directly activated after virus infection and functions as a key activator of the intermediate/early alpha/beta interferon (IFN) genes as well as the RANTES chemokine gene.
PubMed 18818105: IRF3 transcription factor induces type I interferons (IFNs) and elicits innate antiviral response. TMEM173 (MITA) is a critical mediator of virus-triggered IRF3 activation and IFN expression.
PubMed 9566918: IRF3 phosphorylation is virus-inducible and results in IRF3 alteration of protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of interferon (IFN)- and IFN-responsive genes.
PubMed 21768204: IRF3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells.
PubMed 21820332: IRF3 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Irf3/Irf7 are resistant to otherwise lethal cerebral malaria. (Demonstrated in mouse)
PubMed 22170100: IRF3 suppresses neuroinflammation through regulation of immunomodulatory MIR155 microRNA expression in astrocytes.
PubMed 22593165: HIV accessory protein Vpu targets IRF3 to endolysosome for proteolytic degradation to avoid antiviral immune responses.
PubMed 23994473: During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
PubMed 25352594: Vpu, an accessory protein encoded by HIV-1, contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis.
PubMed 25505063: Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
PubMed 25792739: Stimulation of TMEM173-dependent IRF3 activation by ultraviolet radiation is due to apoptotic signalling-dependent disruption of ULK1, a pro-autophagic protein that negatively regulates TMEM173.
PubMed 26046437: PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with MB21D1 to initiate an IRF3-dependent innate response
PubMed 26646986: 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (G10) requires STING to trigger IRF3/IFN-associated transcription in human fibroblasts and subsequently blocking replication of Chikungunya virus, Venezuelan Encephalitis virus, and Sindbis virus.
PubMed 26378160: Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.
2017-05-29
IL1A (Homo sapiens) PubMed 25463072: Interleukin-1 (IL1A/IL1B) plays a key role in the interaction between local vessel wall cells and invading monocytes to multiply cholesterol-triggered inflammation in the vessel wall.
PubMed 25474109: IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
PubMed 25964352: CASP4 is a critical regulator of noncanonical inflammasome activation that initiates defence against bacterial pathogens in primary macrophages by mediating cell death and IL1A release
PubMed 26439902: IL1A directly senses DNA damage and acts as signal for genotoxic stress without loss of cell integrity.
2017-05-29
IFIH1 (Homo sapiens) PubMed 16785313: IFIH1 (MDA5) recognizes distinct RNA viruses and plays a major role in the elimination of RNA viruses in vivo.
PubMed 15563593: IFIH1 binds V proteins of paramyxoviruses and this inhibit its activation of the IFNB1 (IFN-beta) promoter.
PubMed 11805321: IFIH1 is a double-stranded RNA-dependent ATPase that contains both a caspase recruitment domain and RNA helicase motifs. IFIH1 may also function as a mediator of interferon (IFN)-induced growth inhibition and/or apoptosis.
PubMed 20107606: IFIH1 is indispensable for sustained expression of IFN in response to paramyxovirus infection and provide the first evidence of MDA5-dependent containment of in vivo infections caused by (-) sense RNA viruses.
PubMed 21245317: IFIH1 is an RNA helicase and is a key component in activating the expression of type I IFN in response to viral infection. Viral mRNA with 5' cap and 3' poly(A) from parainfluenza virus 5 is able to activate IFN expression through RNASEL-IFIH1 signalling pathway.
PubMed 19936053: IFIH1 (MDA5) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
PubMed 21637773: IFIH1 deficiency results in a delayed type I IFN and attenuated type III IFN response to rhinovirus infection, leading to a transient increase in viral titer. Upon recognition of viral dsRNA, IFIH1 synergizes with TLR3 to induce pro-inflammatory signals leading to airways inflammation and hyper-responsiveness. (Demonstrated in murine model)
PubMed 23328395: Paramyxovirus V proteins bind to IFIH1 (MDA5) to disrupt viral RNA recognition and induction of antiviral immunity.
PubMed 24550253: The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
PubMed 25463548: IFIH1 recognizes hepatitis C virus (HCV) to initiate host interferon response during HCV infection.
PubMed 26074083: DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
PubMed 25878102: EFTUD2 is a novel innate immune antiviral regulator that restricts hepatitis C virus infection through a DDX58/IFIH1-mediated, JAK-STAT-independent pathway.
2017-05-29
PRKRA (Homo sapiens) PubMed 25784705: The G3BP1-CAPRIN1-PRKRA complex represents a new mode of PRKRA activation and links stress responses with innate immune activation through PRKRA without a requirement for foreign double-stranded RNA pattern recognition.
PubMed 26608320: A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
PubMed 26454002: DDX3X participates in antiviral innate immunity by controlling translation of PRKRA.
2017-05-29
MIR136 (Homo sapiens) PubMed 26450567: MIR136 exhibits potent antiviral activity against H5N1 influenza A virus and acts as an immune agonist of DDX58.
2017-05-29
Id2 (Mus musculus) PubMed 25902484: Group 3 innate lymphoid cells (ILC3s) can mediate immune surveillance, which constantly maintains a proper microbiota, to facilitate early colonization resistance through an Id2-dependent regulation of Il22.
2017-05-29
Tlr2 (Mus musculus) PubMed 18768838: Tlr2 expression in astrocytes is induced by TNF alpha and NF Kappa B-dependent pathways.
PubMed 18621910: Tlr2 recognition of Staphylococcal peptidoglycan leads to induction of beta-defensin-2.
PubMed 19019963: Tlr2 is involved in Respiratory syncytial virus (RSV) recognition and subsequent innate immune activation by promoting neutrophil migration and dendritic cell activation within the lung.
PubMed 19865078: Tlr4, Tlr2, or Tlr3 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signaling in mucosal epithelial cell lines.
PubMed 9751057: Tlr2 is a signaling receptor that is activated by lipopolysaccharide (LPS) in a response that depends on LPS-binding protein and is enhanced by CD14.
PubMed 10364168: Tlr2 is a signal transducer for soluble Peptidoglycan and lipoteichoic acid (LTA) in addition to LPS.
PubMed 10384090: Tlr2 recognizes Gram-positive bacterial cell wall components, leading to the activation of the innate immune system.
PubMed 10426996: Tlr2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.
PubMed 20167866: TLR2/MyD88/PI3K/Rac1/Akt pathway mediates the activation of LTA-induced mitogen-activated protein kinases (MAPKs), which in turn initiates the activation of NF-kappaB, and ultimately induces cPLA2/COX-2-dependent PGE2 and IL-6 generation.
PubMed 20385881: Tlr2 and Tlr4 activate murine macrophages and this is negatively regulated by a Lyn/PI3K module and promoted by SHIP1.
PubMed 20407745: Tlr2 is a molecular link between increased dietary lipid intake and the regulation of glucose homeostasis, via regulation of energy substrate utilization and tissue inflammation.
PubMed 20422028: Tlr2 activation induces type I interferon responses from endolysosomal compartments where it is translocated to upon ligand engagement.
PubMed 20368346: Tlr2 and Myd88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages.
PubMed 21439957: Tlr1 :: Tlr2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
PubMed 21454596: Tlr2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages.
PubMed 21482737: Tlr2::Tlr6 synergistically interacts with Tlr9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21512004: Tlr2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance.
PubMed 21566133: Tlr2 and Tnfsf11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss.
PubMed 21602496: Tlr2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureusand contributing to retinal innate defence.
PubMed 21698237: Tlr2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida.
PubMed 21862586: Tlr2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and Notch1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages.
PubMed 21873606: Tlr2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
PubMed 22096480: Tlr2 and Tlr4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae.
PubMed 22102818: Tlr2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG).
PubMed 22174456: Tlr2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of Tnf, Il6, and Il12b cytokines by macrophages and upregulates macrophage function.
PubMed 22216191: Mycobacterium abscessus glycopeptidolipid (GPL) prevents Tlr2-mediate induction of Il8 and Defb4a in respiratory epithelial cells. (Demonstrated in human)
PubMed 23994200: Tlr2 is expressed in the enteric nervous system (ENS) and intestinal smooth muscle layers. Its absence induces architectural and neurochemical coding changes in the ENS, leading to gut dysmotility and to higher inflammatory bowel diseases susceptibility
PubMed 25423082: Salmonella enterica serovar Typhimurium ?msbB that possesses a modified lipid A triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased Tlr2 stimulation.
PubMed 25505250: Adaptor proteins Ticam1 and Ticam2 have a novel function in Tlr2-mediated signal transduction.
PubMed 25826367: Retinoic acid treatment enhances Tlr2-dependent Il10 production from T cells and this, in turn, potentiates T regulatory cell generation without the need for activation of antigen presenting cells.
PubMed 25586105: Proline-proline-glutamic acid 57 (PPE57), located on the mycobacterial cell surface, induces a T helper 1 immune response via Tlr2-mediated macrophage functions.
PubMed 26078314: Tlr2 is essential for the immune responses to cholera vaccination.
PubMed 26283364: Staphylococcal superantigen-like protein 3 (SSL3) interferes with Tlr2 activation at two stages. First by binding to Tlr2 and blocking ligand binding and second by interacting with an already formed Tlr2-lipopeptide complex, thus preventing TLR heterodimerization and downstream signalling.
PubMed 26310831: Peli3 is involved in endotoxin tolerance and functions as a negative regulator of Tlr2/4 signalling.
PubMed 26423153: Cytokine activation as a result of Tlr2 stimulation is mediated by the phagosomal trafficking molecule Ap3b1 (AP-3).
2017-05-29
Ifnb1 (Mus musculus) PubMed 21408089: Ifnb1 deficiency results in a partial suppression of the sterol pathway in macrophages during viral infections, thereby linking the regulation of lipid metabolism pathway with interferon anti-viral defence responses.
PubMed 21602824: Ifnb1 secretion is greater upon viable E. coli infection in comparison to heat killed E. coli vaccine or LPS. The induction of Ifnb1 is dependent on Ticam1-Irf3 signalling.
PubMed 22291574: Ifnb1 expression pattern during viral infection is a highly stochastic process influenced by cell-to-cell variability in viral induction processes.
PubMed 22912878: Ifnb1 production is fundamental to the efficient control of Listeria monocytogenes during the early innate phase of infection. NK cells treated with Ifnb1 during early infection were able to reduce bacterial titer in the spleen and significantly improve survival of infected mice.
PubMed 24656046: The noncanonical NFκB pathway regulates histone modifications at the Ifnb1 promoter resulting in attenuated recruitment of Rela and histone demethylase, Kdm4a, to the Ifnb1 promoter. This provides a mechanism for regulating the induction of type I interferons .
PubMed 25517615: The innate immune system plays a role in immunogenic tumour recognition. Tumor-cell-derived DNA triggers Ifnb1 production and dendritic cell activation via Tmem173 and Irf3 cytosolic DNA sensing pathways.
PubMed 26202980: Ifnb1 selectively restricts the transcriptional responses mediated by both the TLRs and the NOD-like receptors in Salmonella enterica serovar Typhimurium infection in macrophages.
PubMed 26416280: Atf3 plays an important role in modulating IFN responses in macrophages by controlling basal and inducible levels of Ifnb1, as well as the expression of genes downstream of IFN signalling.
2017-05-29
Ap3b1 (Mus musculus) PubMed 21045126: Ap3b1 (AP-3), a lysosome-related organelle trafficking and biogenesis protein, is required for the production of pro-inflammatory cytokines in plasmacytoid dendritic cells upon recognition of viral nucleic acids by endosomal Tlr7 or Tlr9.
PubMed 21119105: Ap3b1 is crucial for the trafficking of Tlr9 to specific endosomal compartments for the induction of type I interferon.
PubMed 26423153: Cytokine activation as a result of Tlr2 stimulation is mediated by the phagosomal trafficking molecule Ap3b1 (AP-3).
2017-05-29
Nlrp3 (Mus musculus) PubMed 19362020: Nlrp3 mediated immune responses can be activated by RNA and mice lacking Nlrp3, or other inflammasome components, exhibit increased mortality and a reduced immune response after influenza virus exposure.
PubMed 19362023: Nlrp3(-/-) mice exhibit increased morbidity after infection with a pathogenic influenza A virus correlating with decreased neutrophil and monocyte recruitment and reduced IL-1beta, IL-18, TNF-alpha, IL-6, KC, MIP2, and IFN-alpha production.
PubMed 21278344: Nlrp3 is directly activated by certain antibiotics and plays an important role in the antibiotic-mediated secretion of Il1b. In the case of polymyxin B, Nlrp3 was also required for the neutrophil influx into the peritoneal cavity.
PubMed 21289120: Nlrp3 inflammasome is essential for host defence against influenza and other RNA viruses (i.e. EMCV, VSV).
PubMed 21385879: Nlrp3 recruits adaptor protein Pycard and Casp1 to form an Nlrp3 inflammasome complex in response to Varicella-Zoster Virus (VZV) infection.
PubMed 21439959: Nlrp3 is a component of the inflammasome and is required for inflammation in acute pancreatitis.
PubMed 21602824: Nlrp3 is necessary to illicit Il1b response specific to viable, but not heat-killed, E. coli infections.
PubMed 22174673: Nlrp3 inflammasome plays a role in innate immune responses against mucosal Candida infection. Nlrp3 limits the severity of infection when present in either the hematopoietic or stromal compartments.
PubMed 22295065: Nlrp3/Pycard inflammasome activation following human respiratory syncytial virus infection is dependent on the activation of Tlr2/Myd88/NF-kB and reactive oxygen species/potassium efflux. (Demonstrated in human)
PubMed 22984081: MIR223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production.
PubMed 23809161: Potassium efflux is a common trigger of NLRP3 Inflammasome activation by bacterial toxins and particulate matter
PubMed 24127597: Mitochondrial membrane potential is required for the association of Nlrp3 and Mfn2. Mfns2 is required for the activation of Nlrp3 inflammasomes.
PubMed 24265316: 3, 4-methylenedioxy-β-nitrostyrene is a potent and specific inhibitor of the NLRP3 inflammasome.
PubMed 24549849: Both Nlrp3 and Nlrp1a are important regulators of Toxoplasma proliferation and that IL18 signaling is required to mediate host resistance to acute toxoplasmosis.
PubMed 24692555: Group B streptococcus induces Il1b, and activates the NLRP3 inflammasome by a mechanism that requires hemolysin-mediated lysosomal leakage, which enhances the interaction of bacterial RNA with NLRP3.
PubMed 25689249: Activation of the Nlrp3 inflammasome is detrimental during leishmaniasis. Mice lacking the inflammasome components Nlrp3, Pycard, Casp1 exhibit defective Il1b and Il18 production at the infection site and are resistant to cutaneous Leishmania major infection.
PubMed 26045547: Nlrp3 is a novel molecular target for melatonin which requires Rora to blunt the NFkB/ NLRP3 connection during sepsis.
PubMed 27214553: Uropathogenic Escherichia coli protein TcpC attenuates activation of the Nlrp3 inflammasome by binding both Nlrp3 and Casp1.
PubMed 26305961: Nlrp3 deficiency protects mice from the development of type 1 diabetes by suppressing Th1 responses and impairing T-cell migration to pancreatic islets through the down-regulation of chemokine expression (Ccl5, Cxcl10, Irf1) in islets.
PubMed 26341399: Nlrp3 and Casp2 are required for endoplasmic reticulum stress-induced inflammation.
PubMed 26416893: Impairment of the mitochondrial electron transport chain by rotenone primes Nlrp3 inflammasome activation upon costimulation with ATP.
2017-05-29
Nod2 (Mus musculus) PubMed 18981137: Nod2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity.
PubMed 20679225: Nod2 functions in non-hematopoietic cells of the small intestinal crypts and this is critical for protecting mice from a Th1-driven granulomatous inflammation in the ilum.
PubMed 20685341: Nod2 and Nod1 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila.
PubMed 17705131: Nod2 and Nod1 activation results in substantial secretion of Ccl5 by murine macrophages and induces binding of NF-kappaB subunits to Ccl5 promoter.
PubMed 21072876: Nod2 and Nod1 can detect Legionella pneumophila and these receptors modulate the in vivo pulmonary immune response differently.
PubMed 21199260: Nod2 is both a positive and negative regulator of Tlr4 - the effect it exerts is dependent on the presence of MDP. Nod2 upon engagement with its ligand, MDP, positively regulates Tlr4-mediated signaling; in the absence of MDP, Nod2 negatively regulates the Tlr4 pathway.
PubMed 21236705: Nod2 is a peripheral peptidoglycan intracellular sensor and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis).
PubMed 21108472: Nod2 detects heat-killed Legionella pneumophila and stimulates NFkB and IFN-beta promoter activity. Nod2 deficiency results in increased proinflammatory cytokine expression at 4hrs and greater neutrophil recruitment to the lung.
PubMed 21690088: Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
PubMed 22750073: Nod2 recognition of muramyl dipeptide, a component of bacterial cell walls, improves the barrier function of intestinal epithelial cells.
PubMed 22531915: Nod2 enhances the innate immune response of alveolar macrophages to Mycobacterium tuberculosis in human. (Demonstrated in human)
PubMed 24163408: Nod1 and Nod2 synergize with Tlr4 in dendritic cells to increase IL12 production and enhance invariant natural killer T (iNKT) cell activation, and are important regulators of the IFN gamma response by iNKT cells during S. typhimurium and L. monocytogenes infections.
PubMed 25423082: Salmonella enterica serovar Typhimurium ?msbB that possesses a modified lipid A triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased Tlr2 stimulation.
PubMed 25817335: Nod2 regulates type-1 cytokine responses to Mycobacterium avium but is not required for the control of M. avium infection in vivo.
PubMed 26444420: Leukotriene B4 acts on Nod2 pathway to enhance the immune response against influenza A infection.
2017-05-29
Iltifb (Mus musculus) PubMed 21469124: Iltifb (Il22b) increases the TNF-alpha-dependent induction and secretion of several immune-modulatory molecules such as initial complement factors, antimicrobial peptides and chemokines in primary keratinocytes. Iltifb-mediated induction of innate immunity is crucial for the maintenance of epidermal integrity during infection with Candida albicans. (Demonstrated in human)
PubMed 21874025: Iltifb (Il22) is produced by lymphoid tissue-inducer cells where it regulates the maintenance of colonic lymphoid structures during Citrobacter rodentium infection, a mechanism that bridges the lymphotoxin pathway to mucosal epithelial defense mechanisms.
PubMed 22921121: ILTIFB (IL22) protects intestinal stem cells from inflammatory tissue damage and regulates sensitivity to graft versus host disease. (Demonstrated in human)
PubMed 25395539: Flagellin induces Tlr5-dependent Il22 production and Nlrc4-dependent Il18 production to promote a protective gene expression program in intestinal epithelial cells and elimination of rotavirus-infected cells.
PubMed 25456160: Cxcl16-Cxcr6 crosstalk coordinates the intestinal topography of Il22 secretion required for mucosal defence against Citrobacter rodentium infection.
PubMed 25680273: Il22 augments the expression of Il18 mRNA and inactive precursor protein (proIL-18) in intestinal epithelial cells after Toxoplasma gondii or Citrobacter rodentium infection and maintains the homeostatic amount of proIL-18 in the ileum.
PubMed 26649819: Innate lymphoid cells, potent producers of Il22 after intestinal injury, increase the growth of mouse small intestine organoids in an Il22-dependent fashion.
PubMed 25902484: Group 3 innate lymphoid cells (ILC3s) can mediate immune surveillance, which constantly maintains a proper microbiota, to facilitate early colonization resistance through an Id2-dependent regulation of Il22.
2017-05-29
Tlr9 (Mus musculus) PubMed 11286707: Tlr9 binds CpG DNA and induces dendritic cell maturation in a MyD88-dependent manner in mice.
PubMed 19923461: Tlr9 engages in signalling crosstalk with Tlr4 during activation, and as a result, amplifies the inflammatory response of murine macrophages.
PubMed 17452530: Tlr9, 7, and 3 interact with the endoplasmic reticulum (ER) membrane protein Unc93b and this is essential for proper TLR signaling.
PubMed 21376231: Tlr9 signalling enhances the rate of acidification of the Salmonella-containing phagosome, and this acidification induces the expression of Salmonella pathogenecity genes that are necessary for intracellular survival, growth, and systemic infection. Tlr9 deficiency rescues the high Salmonella susceptibility phenotype observed in Tlr2,Tlr4 double mutant mice.
PubMed 21389263: Tlr9 triggers plasmacytoid dendritic cells in Systemic Lupus Erythematosus patients upon recognition of self-antigens such as neutrophil extracellular traps (NETs). (Demonstrated in human)
PubMed 21402738: Tlr9 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA.
PubMed 21439959: Tlr9 deficiency reduced pancreatic edema, inflammation and pro-Il1b expression in pacreatitis.
PubMed 21482737: Tlr9 synergistically interacts with Tlr2::Tlr6 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21604257: Tlr9 is proteolytically cleaved in the endosome to form a soluble Tlr9 (sTlr9), which inhibits Tlr9-dependent signalling and contributes to the prevention of autoimmune disease.
PubMed 21721026: Tlr9 activation is enhanced by increased levels of circulating histones, serving as a crucial link between initial damage and activation of innate immunity during sterile inflammation
PubMed 21860217: Tlr9 promotes macrophage Hif1a levels, oxidative burst and nitric oxide production in response to group A Streptococcus (GAS), contributing to GAS clearance in vivo in both localized cutaneous and systemic infection models.
PubMed 21947771: Tlr9 is selectively compartmentalized to fungal phagosomes and negatively modulates macrophage anti-fungal effector functions.
PubMed 22342842: Tlr9 expression and signalling capacity oscillates with the circadian clock.
PubMed 22535248: Mitochondrial DNA that escapes from autophagy induces Tlr9 inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy.
PubMed 23071157: TLR9 activation by endogenous self-ligands generated during oxidative stress promotes platelet hyper-reactivity and thrombosis.
PubMed 23142781: Tlr9 contributes to the control of activated endogenous retroviruses (ERVs) and ERV-induced tumours.
PubMed 23752491: The N-terminal region of TLR9 is cleaved in the endolysosome to form an intracellular DNA sensor with the C-terminal TLR9.
PubMed 24270517: Mir126-Kdr axis is an important regulator of the innate response. Mir126 controls the survival and function of plasmacytoid dendritic cells and regulates gene expression of Tlr7, Tlr9, Nfkb1 and Kdr.
PubMed 25600358: Dnase2a is required for Tlr9 activation by bacterial genomic DNA.
PubMed 26957214: Tyrosine phosphorylation is essential for Tlr9 protein stability and signalling.
PubMed 26416273: Tlr9 activation requires a single CpG positioned 4-6 nucleotides from the 5'-end and this activation is augmented by a 5'TCC sequence one to three nucleotides from the CG.
2017-05-29