Genomes and Genes
Gene Symbol: Bcl2l12
Description: BCL2-like 12 (proline rich)
Alias: 2810475P17Rik, 5430429M05Rik, Bcl-L12, Bcl2-L12, bcl-2-like protein 12
- Daffis S, Szretter K, Schriewer J, Li J, Youn S, Errett J, et al. 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 2010;468:452-6 pubmed publisher..Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells. ..
- Daffis S, Samuel M, Keller B, Gale M, Diamond M. Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and -independent mechanisms. PLoS Pathog. 2007;3:e106 pubmed..Collectively, our data suggest that cell-specific IRF-3 responses protect against WNV infection through both IFN-dependent and -independent programs. ..
- Henry T, Brotcke A, Weiss D, Thompson L, Monack D. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J Exp Med. 2007;204:987-94 pubmed..This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses...
- Carrigan S, Junkins R, Yang Y, MacNeil A, Richardson C, Johnston B, et al. IFN regulatory factor 3 contributes to the host response during Pseudomonas aeruginosa lung infection in mice. J Immunol. 2010;185:3602-9 pubmed publisher..aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection. ..
- Schmitz F, Heit A, Guggemoos S, Krug A, Mages J, Schiemann M, et al. Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells. Eur J Immunol. 2007;37:315-27 pubmed..These results demonstrate that TLR-9 activation of mDC and macrophages contributes to antiviral immunity via IRF-1. ..
- Yanai H, Chen H, Inuzuka T, Kondo S, Mak T, Takaoka A, et al. Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. Proc Natl Acad Sci U S A. 2007;104:3402-7 pubmed..These results, together with the dual regulation of IRF5 gene expression by IFN signaling and p53, may provide a new link in the transcriptional network underlying antiviral immunity and tumor suppression. ..
- O Connell R, Saha S, Vaidya S, Bruhn K, Miranda G, Zarnegar B, et al. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med. 2004;200:437-45 pubmed..Thus, our results highlight the disparate roles of type I IFNs during bacterial versus viral infections and stress the importance of proper IFN modulation in host defense. ..
- Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, et al. Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol. 2012;13:659-66 pubmed publisher..The innate immune receptor cross-interference we describe may have implications for infection-associated clinical episodes. ..
- Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005;434:772-7 pubmed..Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7. ..
- Schilte C, Buckwalter M, Laird M, Diamond M, Schwartz O, Albert M. Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection. J Immunol. 2012;188:2967-71 pubmed publisher..These results highlight the interplay between nonimmune and immune cells during Chikungunya virus infection and suggest an important role for nonhematopoietic cells as a critical source of IFN-?/?...
- Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K, Nakao K, et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity. 2000;13:539-48 pubmed..These results demonstrate the essential and distinct roles of thetwo factors, which together ensure the transcriptional efficiency and diversity of IFN-alpha/beta genes for the antiviral response. ..
- Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, et al. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity. 2011;34:352-63 pubmed publisher..However, Viperin was dispensable for the production of type I IFN induced by intracellular nucleic acids. Thus, Viperin mediates its antiviral function via the regulation of the TLR7 and TLR9-IRAK1 signaling axis in pDCs. ..
- You F, Wang P, Yang L, Yang G, Zhao Y, Qian F, et al. ELF4 is critical for induction of type I interferon and the host antiviral response. Nat Immunol. 2013;14:1237-46 pubmed publisher..Thus, in addition to identifying a regulator of innate immune signaling, we uncovered a role for EICE elements in interferon transactivation. ..
- Ge J, Gong Y, Xu Y, Shao F. Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci U S A. 2012;109:6193-8 pubmed publisher..Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection...
- Dogusan Z, Garcia M, Flamez D, Alexopoulou L, Goldman M, Gysemans C, et al. Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways. Diabetes. 2008;57:1236-45 pubmed publisher..PICex and PICin trigger beta-cell apoptosis via the TLR3 pathway or IRF-3 signaling, respectively. Execution of PICin-mediated apoptosis depends on autocrine effects of type I IFNs. ..
- Molle C, Goldman M, Goriely S. Critical role of the IFN-stimulated gene factor 3 complex in TLR-mediated IL-27p28 gene expression revealing a two-step activation process. J Immunol. 2010;184:1784-92 pubmed publisher..These results highlight the complex molecular interplay between TLRs and type I IFNs for the control of IL-27 synthesis. ..
- Chiang E, Dang O, Anderson K, Matsuzawa A, Ichijo H, David M. Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide. J Immunol. 2006;176:5720-4 pubmed..Thus, our results presented here suggest a novel role for ROS and ASK1 in the innate immune response as signaling intermediates in the IRF3 activation pathway. ..
- Sharma S, Campbell A, Chan J, Schattgen S, Orlowski G, Nayar R, et al. Suppression of systemic autoimmunity by the innate immune adaptor STING. Proc Natl Acad Sci U S A. 2015;112:E710-7 pubmed publisher..Collectively these findings reveal an unexpected negative regulatory role for STING, having important implications for STING-directed therapies. ..
- Shen H, Tesar B, Walker W, Goldstein D. Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation. J Immunol. 2008;181:1849-58 pubmed..In sum, in our experimental systems, TRIF signaling plays a more important role in LPS-induced macrophage activation than in DC activation. ..
- Taylor K, Woods T, Winkler C, Carmody A, Peterson K. Age-dependent myeloid dendritic cell responses mediate resistance to la crosse virus-induced neurological disease. J Virol. 2014;88:11070-9 pubmed publisher..Thus, this study demonstrates a reason for susceptibility to LACV infection in young animals and shows that early therapeutic treatment in young animals can prevent neurological disease. ..
- Lee H, Komano J, Saitoh Y, Yamaoka S, Kozaki T, Misawa T, et al. Zinc-finger antiviral protein mediates retinoic acid inducible gene I-like receptor-independent antiviral response to murine leukemia virus. Proc Natl Acad Sci U S A. 2013;110:12379-84 pubmed publisher..Thus, ZAP is a unique member of the cytosolic RNA-sensing PRR family that targets and eliminates intracellular RNA viruses independently of TLR and RLR family members. ..
- Gill N, Deacon P, Lichty B, Mossman K, Ashkar A. Induction of innate immunity against herpes simplex virus type 2 infection via local delivery of Toll-like receptor ligands correlates with beta interferon production. J Virol. 2006;80:9943-50 pubmed..Results from these in vivo studies clearly suggest a strong correlation between IFN-beta production and innate antiviral immunity against HSV-2. ..
- Carow B, Ye X, Gavier Widen D, Bhuju S, Oehlmann W, Singh M, et al. Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent manner. J Biol Chem. 2011;286:26873-87 pubmed publisher..tuberculosis clearance early after infection in vivo in an IFN-?-dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation. ..
- Schwandt T, Schumak B, Gielen G, Jüngerkes F, Schmidbauer P, Klocke K, et al. Expression of type I interferon by splenic macrophages suppresses adaptive immunity during sepsis. EMBO J. 2012;31:201-13 pubmed publisher..Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis. ..
- Imai Y, Kuba K, Neely G, Yaghubian Malhami R, Perkmann T, Van Loo G, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133:235-49 pubmed publisher..Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI. ..
- Johnson J, Molle C, Aksoy E, Goldman M, Goriely S, Willems F. A conventional protein kinase C inhibitor targeting IRF-3-dependent genes differentially regulates IL-12 family members. Mol Immunol. 2011;48:1484-93 pubmed publisher..Collectively, these data identify cPKCs as critical components that control IRF-3-dependent IL-12p35 and IL-27p28 gene expression downstream of TLR3 and TLR4. ..
- Spann K, Loh Z, Lynch J, Ullah A, Zhang V, Baturcam E, et al. IRF-3, IRF-7, and IPS-1 promote host defense against acute human metapneumovirus infection in neonatal mice. Am J Pathol. 2014;184:1795-806 pubmed publisher..In the absence of a robust type I IFN-?/? response, targeting the IPS-1 signaling pathway may limit the overexuberant inflammatory response that occurs as a consequence of viral persistence. ..
- Keck S, Muller I, Fejer G, Savic I, Tchaptchet S, Nielsen P, et al. Absence of TRIF signaling in lipopolysaccharide-stimulated murine mast cells. J Immunol. 2011;186:5478-88 pubmed publisher..These results show how the response to the same microbial ligand using the same receptor can be regulated in different cell types of the innate immune system. ..
- Weiss G, Maaetoft Udsen K, Stifter S, Hertzog P, Goriely S, Thomsen A, et al. MyD88 drives the IFN-? response to Lactobacillus acidophilus in dendritic cells through a mechanism involving IRF1, IRF3, and IRF7. J Immunol. 2012;189:2860-8 pubmed publisher..acidophilus induces IFN-? independently of the receptors typically used by bacteria, as it requires MyD88, Syk, and PI3K signaling and phagosomal processing to activate IRF1 and IRF3/IRF7 and thereby the release of IFN-?. ..
- Jaillon S, Moalli F, Ragnarsdottir B, Bonavita E, Puthia M, Riva F, et al. The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity. 2014;40:621-32 pubmed publisher..These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs. ..
- Warzée B, Mesnil C, Hober D, Caloone D, Pirottin D, Garigliany M, et al. Viral induction of Zac1b through TLR3- and IRF3-dependent pathways. Mol Immunol. 2010;48:119-27 pubmed publisher..In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated. ..
- Chang E, Guo B, Doyle S, Cheng G. Cutting edge: involvement of the type I IFN production and signaling pathway in lipopolysaccharide-induced IL-10 production. J Immunol. 2007;178:6705-9 pubmed..Our findings suggest a novel anti-inflammatory role for the type I IFN production and signaling pathway in regulating LPS response in bone marrow-derived macrophages. ..
- Negishi H, Miki S, Sarashina H, Taguchi Atarashi N, Nakajima A, Matsuki K, et al. Essential contribution of IRF3 to intestinal homeostasis and microbiota-mediated Tslp gene induction. Proc Natl Acad Sci U S A. 2012;109:21016-21 pubmed publisher..This newly identified intestinal gene regulatory mechanism, wherein IRF3 activated by microbiota-derived nucleic acids plays a critical role in intestinal homeostasis, may have clinical implication in colonic inflammatory disorders. ..
- Ma F, Li B, Yu Y, Iyer S, Sun M, Cheng G. Positive feedback regulation of type I interferon by the interferon-stimulated gene STING. EMBO Rep. 2015;16:202-12 pubmed publisher..Thus, our study demonstrates that STING is an interferon-stimulated gene (ISG) and its induction is crucial for the IFN-I positive feedback loop. ..
- Moore T, Kumm P, Brown D, Petro T. Interferon response factor 3 is crucial to poly-I:C induced NK cell activity and control of B16 melanoma growth. Cancer Lett. 2014;346:122-8 pubmed publisher..Thus, IRF3 is a key factor controlling melanoma growth through NK-cell activities, especially during poly-I:C therapy. ..
- Ouyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochem Biophys Res Commun. 2007;354:1045-51 pubmed..Thus, our findings offer a mechanistic insight into TLR synergy, revealing the hitherto unknown cross talk between the MyD88 and TRIF pathways for a robust TLR-mediated activation of the immune system. ..
- Beisner D, Ch en I, Kolla R, Hoffmann A, Hedrick S. Cutting edge: innate immunity conferred by B cells is regulated by caspase-8. J Immunol. 2005;175:3469-73 pubmed..The activation of NF-kappaB or IFN regulatory factor 3 was found to be unaffected by the loss of caspase-8, implicating it in a novel pathway important for some forms of innate immunity mediated by B cells. ..
- Fischer H, Lutay N, Ragnarsdottir B, Yadav M, Jonsson K, Urbano A, et al. Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection. PLoS Pathog. 2010;6:e1001109 pubmed publisher..Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response...
- Miller J, Maylor Hagen H, Ma Y, Weis J, Weis J. The Lyme disease spirochete Borrelia burgdorferi utilizes multiple ligands, including RNA, for interferon regulatory factor 3-dependent induction of type I interferon-responsive genes. Infect Immun. 2010;78:3144-53 pubmed publisher..These findings suggest that B. burgdorferi invasion of joint tissue and the resultant type I IFN induction associated with Lyme arthritis development may involve multiple triggering ligands. ..
- Kang S, Liang H, Reizis B, Locksley R. Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells. Immunity. 2008;29:819-33 pubmed publisher..Thus, spatial organization of the immune response by DCs between 6 and 24 hr ensures functional activation of innate cells, which restricts pathogens before adaptive immunity is fully activated. ..
- Carpentier P, Williams B, Miller S. Distinct roles of protein kinase R and toll-like receptor 3 in the activation of astrocytes by viral stimuli. Glia. 2007;55:239-52 pubmed..The activation of astrocytes through these different pathways has implications for the initiation and progression of viral encephalitis and demyelinating diseases such as multiple sclerosis. ..
- Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D, et al. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A. 2009;106:14978-83 pubmed publisher..Thus, NF-kappaB p50 is a key component in the orchestration of M2-driven inflammatory reactions. ..
- Takaki H, Takeda M, Tahara M, Shingai M, Oshiumi H, Matsumoto M, et al. The MyD88 pathway in plasmacytoid and CD4+ dendritic cells primarily triggers type I IFN production against measles virus in a mouse infection model. J Immunol. 2013;191:4740-7 pubmed publisher..Induction of type I IFN in these DC subsets was abolished by the MyD88 inhibitory peptide. Thus, production of type I IFN occurs via the MyD88-dependent and MAVS-independent signaling pathway during MV infection. ..
- Farlik M, Reutterer B, Schindler C, Greten F, Vogl C, Muller M, et al. Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity. 2010;33:25-34 pubmed publisher..Thus, STATs and NF-kappaB cooperate through pol II promoter recruitment and the phosphorylation of its CTD, respectively, as a prerequisite for productive elongation of iNOS mRNA. ..
- Biondo C, Signorino G, Costa A, Midiri A, Gerace E, Galbo R, et al. Recognition of yeast nucleic acids triggers a host-protective type I interferon response. Eur J Immunol. 2011;41:1969-79 pubmed publisher..These data suggest that recognition of yeast nucleic acids by TLR7 and TLR9 triggers a host-protective IFN-?/? response. ..
- Molle C, Nguyen M, Flamand V, Renneson J, Trottein F, De Wit D, et al. IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory factor 3. J Immunol. 2007;178:7607-15 pubmed..Furthermore, chromatin immunoprecipitation studies demonstrate that IRF3 is recruited to the endogenous p28 promoter in TLR4-stimulated human DCs. We conclude that IRF3 activation is a master switch for IL-27 synthesis. ..
- Schuessler A, Funk A, Lazear H, Cooper D, Torres S, Daffis S, et al. West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response. J Virol. 2012;86:5708-18 pubmed publisher..The results define a novel function of sfRNA in flavivirus pathogenesis via its contribution to viral evasion of the type I interferon response. ..
- Nakajima A, Nishimura K, Nakaima Y, Oh T, Noguchi S, Taniguchi T, et al. Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutation concomitant with the disruption of the juxtaposed Irf3 gene. Proc Natl Acad Sci U S A. 2009;106:12448-52 pubmed publisher..The Bcl2l12 gene, encoding Bcl2L12 protein structurally related to the Bcl-2 family, was found to almost overlap with the ..
- Rathinam V, Jiang Z, Waggoner S, Sharma S, Cole L, Waggoner L, et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol. 2010;11:395-402 pubmed publisher..Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity...
- Liu Y, Zeng L, Tian A, Bomkamp A, Rivera D, Gutman D, et al. Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3. J Immunol. 2012;189:4630-9 pubmed publisher..Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN. ..
- Baccarella A, Fontana M, Chen E, Kim C. Toll-like receptor 7 mediates early innate immune responses to malaria. Infect Immun. 2013;81:4431-42 pubmed publisher..Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses. ..
- del Fresno C, Soulat D, Roth S, Blazek K, Udalova I, Sancho D, et al. Interferon-? production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity. 2013;38:1176-86 pubmed publisher..albicans-infected mice with Syk-deficient DCs. These data indicate that Dectin-induced IFN-? production by renal DCs is crucial for defense against C. albicans infection. ..
- Kamran N, Takai Y, Miyoshi J, Biswas S, Wong J, Gasser S. Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells. PLoS ONE. 2013;8:e54406 pubmed publisher..Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines. ..
- Jakobsen M, Bak R, Andersen A, Berg R, Jensen S, Tengchuan J, et al. IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci U S A. 2013;110:E4571-80 pubmed publisher..Thus, IFI16 is a sensor for DNA forms produced during the lentiviral replication cycle and regulates HIV-1 replication in macrophages. ..
- Takemura N, Kawasaki T, Kunisawa J, Sato S, Lamichhane A, Kobiyama K, et al. Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nat Commun. 2014;5:3492 pubmed publisher..An inhibitor of TLR3-RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. ..
- Okabe Y, Kawane K, Nagata S. IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation. Eur J Immunol. 2008;38:3150-8 pubmed publisher..These results indicate that the mammalian chromosomal DNA that accumulates in macrophages due to inefficient degradation activates genes in both IRF3/IRF7-dependent and -independent manners. ..
- Sander L, Davis M, Boekschoten M, Amsen D, Dascher C, Ryffel B, et al. Detection of prokaryotic mRNA signifies microbial viability and promotes immunity. Nature. 2011;474:385-9 pubmed publisher..Detection of vita-PAMPs triggers a state of alert not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines. ..
- Kobayashi H, Kobayashi C, Nakamura Ishizu A, Karigane D, Haeno H, Yamamoto K, et al. Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING. Cell Rep. 2015;11:71-84 pubmed publisher..Our results define machinery underlying the dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling. ..
- Lazear H, Lancaster A, Wilkins C, Suthar M, Huang A, Vick S, et al. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling. PLoS Pathog. 2013;9:e1003118 pubmed publisher..Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5. ..
- Yount J, Gitlin L, Moran T, LOPEZ C. MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. J Immunol. 2008;180:4910-8 pubmed..The unique mechanism by which DI particles trigger the maturation of DCs represents a novel strategy that could be further exploited for the development of potent adjuvant molecules...
- Walker W, Bozzi A, Goldstein D. IRF3 contributes to sepsis pathogenesis in the mouse cecal ligation and puncture model. J Leukoc Biol. 2012;92:1261-8 pubmed publisher..Finally, we show that IRF3 is activated in macrophages cultured with live or sonicated commensal bacteria. These results demonstrate that IRF3 plays a detrimental role in this mouse model of sepsis. ..
- Oshiumi H, Okamoto M, Fujii K, Kawanishi T, Matsumoto M, Koike S, et al. The TLR3/TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection. J Immunol. 2011;187:5320-7 pubmed publisher..These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection...
- Temizoz B, Kuroda E, Ohata K, Jounai N, Ozasa K, Kobiyama K, et al. TLR9 and STING agonists synergistically induce innate and adaptive type-II IFN. Eur J Immunol. 2015;45:1159-69 pubmed publisher..Thus, the combination of CpG ODN and a STING ligand may offer therapeutic application as a potent type-II IFN inducer. ..
- Negishi H, Matsuki K, Endo N, Sarashina H, Miki S, Matsuda A, et al. Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor-mediated enhancement of the MKP-IRF3 axis. Proc Natl Acad Sci U S A. 2013;110:19884-9 pubmed publisher..This study, therefore, reveals a hitherto unrecognized and important contribution of a beneficial innate signaling interference against bacterial infections. ..
- Xu P, Bailey Bucktrout S, Xi Y, Xu D, Du D, Zhang Q, et al. Innate antiviral host defense attenuates TGF-? function through IRF3-mediated suppression of Smad signaling. Mol Cell. 2014;56:723-37 pubmed publisher..We present a mechanism of regulation of TGF-? signaling by the antiviral defense, with evidence for its role in immune tolerance and cancer cell behavior. ..
- Rongvaux A, Jackson R, Harman C, Li T, West A, de Zoete M, et al. Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA. Cell. 2014;159:1563-77 pubmed publisher..This mechanism provides a dual control, which determines whether mitochondria initiate an immunologically silent or a proinflammatory type of cell death...
- Stetson D, Ko J, Heidmann T, Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell. 2008;134:587-98 pubmed publisher..These findings reveal a cell-intrinsic mechanism for initiation of autoimmunity, implicate the ISD pathway as the cause of AGS, and suggest an unanticipated contribution of endogenous retroelements to autoimmunity. ..
- Ebihara T, Azuma M, Oshiumi H, Kasamatsu J, Iwabuchi K, Matsumoto K, et al. Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation. J Exp Med. 2010;207:2675-87 pubmed publisher..We identify a new pathway for mDC-NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule. ..
- Unterholzner L, Keating S, Baran M, Horan K, Jensen S, Sharma S, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11:997-1004 pubmed publisher..IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-? induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs). ..
- Rothfuchs A, Trumstedt C, Mattei F, Schiavoni G, Hidmark A, Wigzell H, et al. STAT1 regulates IFN-alpha beta- and IFN-gamma-dependent control of infection with Chlamydia pneumoniae by nonhemopoietic cells. J Immunol. 2006;176:6982-90 pubmed..In summary, we demonstrate that STAT1 mediates a cooperative effect of IFN-alphabeta and IFN-gamma on nonhemopoietic cells, resulting in protection against C. pneumoniae. ..
- Trumstedt C, Eriksson E, Lundberg A, Yang T, Yan Z, Wigzell H, et al. Role of IRAK4 and IRF3 in the control of intracellular infection with Chlamydia pneumoniae. J Leukoc Biol. 2007;81:1591-8 pubmed..pneumoniae-induced IFN-alpha and IFN-gamma secretion and bacterial growth. IRAK4 and IRF3 are redundant for infection-induced NF-kappaB activation, which is regulated by TRAF6. ..
- Soudja S, Ruiz A, Marie J, Lauvau G. Inflammatory monocytes activate memory CD8(+) T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion. Immunity. 2012;37:549-62 pubmed publisher..Thus, inflammatory monocyte-derived IL-18 and IL-15 are critical to initiate memory CD8(+) T and NK lymphocytes differentiation into antimicrobial effector cells. ..
- Takaki H, Honda K, Atarashi K, Kobayashi F, Ebihara T, Oshiumi H, et al. MAVS-dependent IRF3/7 bypass of interferon ?-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells. Mol Immunol. 2014;57:100-10 pubmed publisher..We also showed the importance of IL-10-producing CD4(+) T cells induced by MV-infected BMDCs in vitro, which may account for immune modulation due to the functional aberration of DCs...
- Prantner D, Sikes J, Hennings L, Savenka A, Basnakian A, Nagarajan U. Interferon regulatory transcription factor 3 protects mice from uterine horn pathology during Chlamydia muridarum genital infection. Infect Immun. 2011;79:3922-33 pubmed publisher..These data suggest that IRF3 has a role in protection from uterine horn pathology that is independent of its function in IFN-? expression...
- Patel A, Lee Lewis H, Hughes Hanks J, Lewis C, Anderson D. Opposing roles for interferon regulatory factor-3 (IRF-3) and type I interferon signaling during plague. PLoS Pathog. 2012;8:e1002817 pubmed publisher..Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-? production. ..
- Stegh A, Brennan C, Mahoney J, Forloney K, Jenq H, Luciano J, et al. Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor. Genes Dev. 2010;24:2194-204 pubmed publisher..b>Bcl2L12 (for Bcl2-like 12) is a cytoplasmic and nuclear protein that is overexpressed in primary GBM and functions to ..
- Oganesyan G, Saha S, Pietras E, Guo B, Miyahira A, Zarnegar B, et al. IRF3-dependent type I interferon response in B cells regulates CpG-mediated antibody production. J Biol Chem. 2008;283:802-8 pubmed