{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:14:59Z","timestamp":1791292499119,"version":"4.1.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Chikungunya virus (CHIKV) is the etiological agent of chikungunya fever (CHIKF), a self-limiting disease characterized by myalgia and severe acute or chronic arthralgia. CHIKF is associated with immunopathology and high levels of pro-inflammatory factors. CHIKV is known to have a wide range of tropism in human cell types, including keratinocytes, fibroblasts, endothelial cells, monocytes, and macrophages. Previously, we reported that CHIKV-infected monocytes-derived macrophages (MDMs) express high levels of interleukin 27 (IL27), a heterodimeric cytokine consisting of IL27p28 and EBI3 subunits, that triggers JAK-STAT signaling and promotes pro-inflammatory and antiviral response, in interferon (IFN)-independent manner. Based on the transcriptomic analysis, we now report that induction of IL27-dependent pro-inflammatory and antiviral response in CHIKV-infected MDMs relies on two signaling pathways: an early signal dependent on recognition of CHIKV-PAMPs by TLR1\/2-MyD88 to activate NF-\u03baB-complex that induces the expression of EBI3 mRNA; and second signaling dependent on the recognition of intermediates of CHIKV replication (such as dsRNA) by TLR3-TRIF, to activate IRF1 and the induction of IL27p28 mRNA expression. Both signaling pathways were required to produce a functional IL27 protein involved in the induction of ISGs, including antiviral proteins, cytokines, CC- and CXC- chemokines in an IFN-independent manner in MDMs. Furthermore, we reported that activation of TLR4 by LPS, both in human MDMs and murine BMDM, results in the induction of both subunits of IL27 that trigger strong IL27-dependent pro-inflammatory and antiviral response independent of IFNs signaling. Our findings are a significant contribution to the understanding of molecular and cellular mechanisms of CHIKV infection.<\/jats:p>","DOI":"10.3389\/fcell.2022.812110","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T05:41:47Z","timestamp":1644385307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Synergistic Effects of Toll-Like Receptor 1\/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages"],"prefix":"10.3389","volume":"10","author":[{"given":"Juan Felipe","family":"Vald\u00e9s-L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geysson J.","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Urcuqui-Inchima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.cytogfr.2012.10.001","article-title":"The Emerging Role of Interleukin 27 in Inflammatory Arthritis and Bone Destruction","volume":"24","author":"Adamopoulos","year":"2013","journal-title":"Cytokine Growth Factor. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/35021228","article-title":"Toll-like Receptors in the Induction of the Innate Immune Response","volume":"406","author":"Aderem","year":"2000","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1038\/s41467-020-16849-7","article-title":"TLR2 on Blood Monocytes Senses Dengue Virus Infection and its Expression Correlates with Disease Pathogenesis","volume":"11","author":"Aguilar-Brise\u00f1o","year":"2020","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/srep12524","article-title":"Transcriptional Profiling of Macrophages Derived from Monocytes and iPS Cells Identifies a Conserved Response to LPS and Novel Alternative Transcription","volume":"5","author":"Alasoo","year":"2015","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1084\/jem.20100064","article-title":"IL-27 Supports Germinal center Function by Enhancing IL-21 Production and the Function of T Follicular Helper Cells","volume":"207","author":"Batten","year":"2010","journal-title":"JME"},{"key":"B6","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1086\/590003","article-title":"Persistent Arthralgia Associated with Chikungunya Virus: A Study of 88 Adult Patients on Reunion Island","volume":"47","author":"Borgherini","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.4049\/jimmunol.1102914","article-title":"Complement Activation Product C5a Is a Selective Suppressor of TLR4-Induced, but Not TLR3-Induced, Production of IL-27(p28) from Macrophages","volume":"188","author":"Bosmann","year":"2012","journal-title":"J.I."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2018.02148","article-title":"Herpes Simplex Virus Type 1 Engages Toll like Receptor 2 to Recruit Macrophages during Infection of Enteric Neurons","volume":"9","author":"Brun","year":"2018","journal-title":"Front. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/545493","article-title":"Cytokines as Biomarkers in Rheumatoid Arthritis","volume":"2014","author":"Burska","year":"2014","journal-title":"Mediators Inflamm."},{"key":"B10","doi-asserted-by":"publisher","first-page":"922","DOI":"10.4049\/jimmunol.180.2.922","article-title":"IL-27 Induces a Th1 Immune Response and Susceptibility to Experimental Arthritis","volume":"180","author":"Cao","year":"2008","journal-title":"J. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.4049\/jimmunol.1300252","article-title":"IL-27, a Cytokine, and IFN-\u039b1, a Type III IFN, Are Coordinated to Regulate Virus Replication through Type I IFN","volume":"192","author":"Cao","year":"2014","journal-title":"J.I."},{"key":"B12","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1189\/jlb.0207128","article-title":"Toll-like Receptors 1 and 6 Are Involved in TLR2-Mediated Macrophage Activation by Hepatitis C Virus Core and NS3 Proteins","volume":"82","author":"Chang","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/infdis\/jiq042","article-title":"Persistent Arthralgia Induced by Chikungunya Virus Infection Is Associated with Interleukin-6 and Granulocyte Macrophage colony-stimulating Factor","volume":"203","author":"Chow","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1128\/mcb.10.4.1498-1506.1990","article-title":"Regulation of Tumor Necrosis Factor Alpha Transcription in Macrophages: Involvement of Four Kappa B-like Motifs and of Constitutive and Inducible Forms of NF-Kappa B","volume":"10","author":"Collart","year":"1990","journal-title":"Mol. Cel Biol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fimmu.2018.00022","article-title":"High-Resolution Mapping and Dynamics of the Transcriptome, Transcription Factors, and Transcription Co-factor Networks in Classically and Alternatively Activated Macrophages","volume":"9","author":"Das","year":"2018","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1446","DOI":"10.1371\/journal.pntd.0001446","article-title":"Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia","volume":"6","author":"Dupuis-Maguiraga","year":"2012","journal-title":"Plos Negl. Trop. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1182\/blood-2006-02-001578","article-title":"Noninfectious Papilloma Virus-like Particles Inhibit HIV-1 Replication: Implications for Immune Control of HIV-1 Infection by IL-27","volume":"109","author":"Fakruddin","year":"2007","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"105619","DOI":"10.1016\/j.actatropica.2020.105619","article-title":"Chikungunya Virus Infection Induces Differential Inflammatory and Antiviral Responses in Human Monocytes and Monocyte-Derived Macrophages","volume":"211","author":"Felipe","year":"2020","journal-title":"Acta Tropica"},{"key":"B19","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3389\/fgene.2020.00541","article-title":"MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia","volume":"11","author":"Fernandez","year":"2020","journal-title":"Front. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1089\/jir.2009.0093","article-title":"Interleukin-27, an Anti-HIV-1 Cytokine, Inhibits Replication of Hepatitis C Virus","volume":"30","author":"Frank","year":"2010","journal-title":"J. Interferon Cytokine Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1089\/vbz.2014.1710","article-title":"Chikungunya Virus Pathogenesis and Immunity","volume":"15","author":"Gasque","year":"2015","journal-title":"Vector-Borne Zoonotic Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/nri3713","article-title":"Assembly and Localization of Toll-like Receptor Signalling Complexes","volume":"14","author":"Gay","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"R88","DOI":"10.1186\/ar1955","article-title":"Interleukin-15 and Interferon- \u03b3 Participate in the Cross-Talk between Natural Killer and Monocytic Cells Required for Tumour Necrosis Factor Production Research Article","volume":"8","author":"Gonz\u00e1lez-\u00c1lvaro","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.actatropica.2019.05.005","article-title":"IL-27 in Patients with Chikungunya Fever: A Possible Chronicity Biomarker?","volume":"196","author":"Gualberto Cavalcanti","year":"2019","journal-title":"Acta Tropica"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/JVI.02196-17","article-title":"Interleukin-27R Signaling Mediates Early Viral Containment and Impacts Innate and Adaptive Immunity after Chronic Lymphocytic Choriomeningitis Virus Infection","volume":"92","author":"Harker","year":"2018","journal-title":"J. Virol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple Combinations of Lineage-Determining Transcription Factors Prime Cis-Regulatory Elements Required for Macrophage and B Cell Identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cel"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2015.00426","article-title":"HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation","volume":"6","author":"Henrick","year":"2015","journal-title":"Front. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"24","DOI":"10.15252\/emmm.201404459","article-title":"Loss of TLR3 Aggravates CHIKV Replication and Pathology Due to an Altered Virus\u2010specific Neutralizing Antibody Response","volume":"7","author":"Her","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"6231","DOI":"10.1128\/mcb.13.10.6231","article-title":"Characterization of a Functional NF-Kappa B Site in the Human Interleukin 1 Beta Promoter: Evidence for a Positive Autoregulatory Loop","volume":"13","author":"Hiscott","year":"1993","journal-title":"Mol. Cel. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/intimm\/dxm139","article-title":"IL-27 Inhibits the Development of Regulatory T Cells via STAT3","volume":"20","author":"Huber","year":"2007","journal-title":"Int. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.immuni.2012.11.003","article-title":"Interleukin-27: Balancing Protective and Pathological Immunity","volume":"37","author":"Hunter","year":"2012","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"INNATE IMMUNE RECOGNITION","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1016\/j.micinf.2009.09.003","article-title":"Immuno-biology of Chikungunya and Implications for Disease Intervention","volume":"11","author":"Kam","year":"2009","journal-title":"Microbes Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like Receptor Signaling Pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/s41423-019-0235-z","article-title":"Macrophages Are the Primary Effector Cells in IL-7-induced Arthritis","volume":"17","author":"Kim","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4984","DOI":"10.1038\/s41598-019-41478-6","article-title":"IL-27 Promotes NK Cell Effector Functions via Maf-Nrf2 Pathway during Influenza Infection","volume":"9","author":"Kumar","year":"2019","journal-title":"Sci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6137","DOI":"10.1128\/mcb.13.10.6137","article-title":"NF-kappa B Subunit-specific Regulation of the Interleukin-8 Promoter","volume":"13","author":"Kunsch","year":"1993","journal-title":"Mol. Cel. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"F38","DOI":"10.1152\/ajprenal.00590.2010","article-title":"Toll-like Receptor 4 Activates NF-\u039ab and MAP Kinase Pathways to Regulate Expression of Proinflammatory COX-2 in Renal Medullary Collecting Duct Cells","volume":"302","author":"K\u00fcper","year":"2012","journal-title":"Am. J. Physiology-Renal Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/80833","article-title":"Pattern Recognition Receptors TLR4 and CD14 Mediate Response to Respiratory Syncytial Virus","volume":"1","author":"Kurt-jones","year":"2000","journal-title":"Nat. Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"eaay3245","DOI":"10.1126\/sciadv.aay3245","article-title":"IL-27 Signaling Activates Skin Cells to Induce Innate Antiviral Proteins and Protects against Zika Virus Infection","volume":"6","author":"Kwock","year":"2020","journal-title":"Sci. Adv."},{"key":"B41","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.1365-3083.2007.02040.x","article-title":"Expression and Regulation of the CC-Chemokine Ligand 20 during Human Tuberculosis","volume":"67","author":"Lee","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.jmb.2013.11.024","article-title":"Toll-like Receptors in Antiviral Innate Immunity","volume":"426","author":"Lester","year":"2014","journal-title":"J. Mol. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-422X-9-114","article-title":"Poly (I:C), an Agonist of Toll-like Receptor-3, Inhibits Replication of the Chikungunya Virus in BEAS-2B Cells","volume":"9","author":"Li","year":"2012","journal-title":"Virol. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1128\/mcb.10.5.2327-2334.1990","article-title":"Activation of Interleukin-6 Gene Expression through the NF-Kappa B Transcription Factor","volume":"10","author":"Libermann","year":"1990","journal-title":"Mol. Cel Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cels.2017.06.014","article-title":"Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages","volume":"5","author":"Lin","year":"2017","journal-title":"Cel Syst."},{"key":"B46","doi-asserted-by":"publisher","first-page":"11899","DOI":"10.1074\/jbc.M111.308064","article-title":"Influenza A Virus Induces Interleukin-27 through Cyclooxygenase-2 and Protein Kinase A Signaling","volume":"287","author":"Liu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"15047","DOI":"10.1073\/pnas.2536517100","article-title":"IL-27 Regulates IL-12 Responsiveness of Naive CD4+ T Cells through Stat1-dependent and -independent Mechanisms","volume":"100","author":"Lucas","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nature04946","article-title":"Intracellular Pattern Recognition Receptors in the Host Response","volume":"442","author":"Meylan","year":"2006","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","first-page":"3972","DOI":"10.1016\/j.celrep.2020.03.008","article-title":"TLR4-Mediated Pathway Triggers Interferon-independent G0 Arrest and Antiviral SAMHD1 Activity in Macrophages","volume":"30","author":"Mlcochova","year":"2020","journal-title":"Cel Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"7607","DOI":"10.4049\/jimmunol.178.12.7607","article-title":"IL-27 Synthesis Induced by TLR Ligation Critically Depends on IFN Regulatory Factor 3","volume":"178","author":"Molle","year":"2007","journal-title":"J. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.4049\/jimmunol.175.3.1686","article-title":"Augmentation of Effector CD8+ T Cell Generation with Enhanced Granzyme B Expression by IL-27","volume":"175","author":"Morishima","year":"2005","journal-title":"J. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"5258","DOI":"10.1128\/mcb.15.10.5258","article-title":"Regulation of Interleukin 12 P40 Expression through an NF-Kappa B Half-Site","volume":"15","author":"Murphy","year":"1995","journal-title":"Mol. Cel Biol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.4049\/jimmunol.0900568.IL-27","article-title":"IL-27 Is a Key Regulator of IL-10 and IL-17 Production by Human CD4+ T Cells","volume":"183","author":"Murugaiyan","year":"2009","journal-title":"J. Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF- B Family of Transcription Factors and its Regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1074\/jbc.271.3.1651","article-title":"Glucocorticoid-mediated Gene Suppression of Rat Cytokine-Induced Neutrophil Chemoattractant CINC\/gro, a Member of the Interleukin-8 Family, through Impairment of NF-\u039ab Activation","volume":"271","author":"Ohtsuka","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1089\/dna.2005.24.614","article-title":"Interferon-\u03b2 Induction through Toll-like Receptor 3 Depends on Double-Stranded RNA Structure","volume":"24","author":"Okahira","year":"2005","journal-title":"DNA Cel Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e00179","DOI":"10.1128\/JVI.00179-17","article-title":"Ebolaviruses Associated with Differential Pathogenicity Induce Distinct Host Responses in Human Macrophages","volume":"91","author":"Olejnik","year":"2017","journal-title":"J. Virol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2012.00079","article-title":"The Role of TLR2 in Infection and Immunity","volume":"3","author":"Oliveira-nascimento","year":"2012","journal-title":"Front. Immun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jviromet.2004.11.002","article-title":"Development of a TaqMan RT-PCR Assay without RNA Extraction Step for the Detection and Quantification of African Chikungunya Viruses","volume":"124","author":"Pastorino","year":"2005","journal-title":"J. Virol. Methods"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.4049\/jimmunol.172.4.2225","article-title":"WSX-1 and Glycoprotein 130 Constitute a Signal-Transducing Receptor for IL-27","volume":"172","author":"Pflanz","year":"2004","journal-title":"J. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/s1074-7613(02)00324-2","article-title":"IL-27, a Heterodimeric Cytokine Composed of EBI3 and P28 Protein, Induces Proliferation of Naive CD4+ T Cells","volume":"16","author":"Pflanz","year":"2002","journal-title":"Immunity"},{"key":"B62","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/imr.12001","article-title":"Structural and Dynamic Determinants of Type I Interferon Receptor Assembly and Their Functional Interpretation","volume":"250","author":"Piehler","year":"2012","journal-title":"Immunol. Rev."},{"key":"B63","doi-asserted-by":"publisher","first-page":"18502","DOI":"10.1073\/pnas.0702388104","article-title":"Transformation of Hematopoietic Cells and Activation of JAK2-V617f by IL-27R, a Component of a Heterodimeric Type I Cytokine Receptor","volume":"104","author":"Pradhan","year":"2007","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.virusres.2014.05.010","article-title":"TLR3 Mediated Innate Immune Response in Mice Brain Following Infection with Chikungunya Virus","volume":"189","author":"Priya","year":"2014","journal-title":"Virus. Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"8391","DOI":"10.1073\/pnas.1424980112","article-title":"CD14 Dependence of TLR4 Endocytosis and TRIF Signaling Displays Ligand Specificity and Is Dissociable in Endotoxin Tolerance","volume":"112","author":"Rajaiah","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B66","doi-asserted-by":"publisher","first-page":"19420","DOI":"10.1073\/pnas.1005793107","article-title":"IL-27 Structural Analysis Demonstrates Similarities with Ciliary Neurotrophic Factor (CNTF) and Leads to the Identification of Antagonistic Variants","volume":"107","author":"Rousseau","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1038\/s41598-017-01600-y","article-title":"Lipopolysaccharide-induced NF-\u039ab Nuclear Translocation Is Primarily Dependent on MyD88, but TNF\u03b1 Expression Requires TRIF and MyD88","volume":"7","author":"Sakai","year":"2017","journal-title":"Sci. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41575-020-0273-0","article-title":"JAK-STAT Pathway Targeting for the Treatment of Inflammatory Bowel Disease","volume":"17","author":"Salas","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"e2137","DOI":"10.1371\/journal.pntd.0002137","article-title":"Chikungunya Virus-Associated Long-Term Arthralgia: A 36-month Prospective Longitudinal Study","volume":"7","author":"Schilte","year":"2013","journal-title":"Plos Negl. Trop. Dis."},{"key":"B70","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/0092-8674(86)90346-6","article-title":"Multiple Nuclear Factors Interact with the Immunoglobulin Enhancer Sequences","volume":"46","author":"Sen","year":"1986","journal-title":"Cell"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.4049\/jimmunol.181.3.1849","article-title":"Dual Signaling of MyD88 and TRIF Is Critical for Maximal TLR4-Induced Dendritic Cell Maturation","volume":"181","author":"Shen","year":"2008","journal-title":"J. Immunol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1172\/jci84417","article-title":"Chikungunya Virus: Epidemiology, Replication, Disease Mechanisms, and Prospective Intervention Strategies","volume":"127","author":"Silva","year":"2017","journal-title":"J. Clin. Invest."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e389","DOI":"10.1371\/journal.pntd.0000389","article-title":"Post-epidemic Chikungunya Disease on Reunion Island: Course of Rheumatic Manifestations and Associated Factors over a 15-Month Period","volume":"3","author":"Sissoko","year":"2009","journal-title":"Plos Negl. Trop. Dis."},{"key":"B74","doi-asserted-by":"publisher","first-page":"e89","DOI":"10.1371\/journal.ppat.0030089","article-title":"Characterization of Reemerging Chikungunya Virus","volume":"3","author":"Sourisseau","year":"2007","journal-title":"Plos Pathog."},{"key":"B75","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.immuni.2006.08.007","article-title":"Type I Interferons in Host Defense","volume":"25","author":"Stetson","year":"2006","journal-title":"Immunity"},{"key":"B76","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/j.1349-7006.2007.00687.x","article-title":"Expression of CCL17 and CCL22 by Latent Membrane Protein 1-positive Tumor Cells in Age-Related Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder","volume":"99","author":"Takegawa","year":"2008","journal-title":"Cancer Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0952-7915(01)00305-3","article-title":"The Interferon-\u0391\/\u03b2 System in Antiviral Responses: a Multimodal Machinery of Gene Regulation by the IRF Family of Transcription Factors","volume":"14","author":"Taniguchi","year":"2002","journal-title":"Curr. Opin. Immunol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/ni774","article-title":"TLR4, but Not TLR2, Mediates IFN-\u03b2-Induced STAT1\u03b1\/\u03b2-dependent Gene Expression in Macrophages","volume":"3","author":"Toshchakov","year":"2002","journal-title":"Nat. Immunol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1089\/jir.2019.0058","article-title":"Chikungunya Virus and Zika Virus, Two Different Viruses Examined with a Common Aim: Role of Pattern Recognition Receptors on the Inflammatory Response","volume":"39","author":"Vald\u00e9s L\u00f3pez","year":"2019","journal-title":"J. Interferon Cytokine Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"104411","DOI":"10.1016\/j.cellimm.2021.104411","article-title":"Interleukin 27 as an Inducer of Antiviral Response against Chikungunya Virus Infection in Human Macrophages","volume":"367","author":"Vald\u00e9s-L\u00f3pez","year":"2021","journal-title":"Cell Immunol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/infdis\/jiq006","article-title":"The Acute Phase of Chikungunya Virus Infection in Humans Is Associated with Strong Innate Immunity and T CD8 Cell Activation","volume":"204","author":"Wauquier","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2814","DOI":"10.4049\/jimmunol.174.5.2814","article-title":"EBV-induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-\u039ab Activation","volume":"174","author":"Wirtz","year":"2005","journal-title":"J. Immunol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"R129","DOI":"10.1186\/ar3067","article-title":"Effects of Inflammatory Cytokine IL-27 on the Activation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis","volume":"12","author":"Wong","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"B84","doi-asserted-by":"publisher","first-page":"161","DOI":"10.3390\/cells7100161","article-title":"Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development","volume":"7","author":"Yap","year":"2018","journal-title":"Cells"},{"key":"B85","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fphar.2020.00129","article-title":"Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges","volume":"11","author":"Ye","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1146\/annurev-immunol-032414-112134","article-title":"The Immunobiology of Interleukin-27","volume":"33","author":"Yoshida","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"21269","DOI":"10.1074\/jbc.M110.100818","article-title":"Activation of IL-27 P28 Gene Transcription by Interferon Regulatory Factor 8 in Cooperation with Interferon Regulatory Factor 1","volume":"285","author":"Zhang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s41590-021-00937-x","article-title":"TLR2 Senses the SARS-CoV-2 Envelope Protein to Produce Inflammatory Cytokines","volume":"22","author":"Zheng","year":"2021","journal-title":"Nat. Immunol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.812110\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T05:41:51Z","timestamp":1644385311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.812110\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":88,"alternative-id":["10.3389\/fcell.2022.812110"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.812110","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]},"article-number":"812110"}}