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Although previous data demonstrated the importance of TLRs and IL-1R signaling events for the establishment of an effective immune response to mycobacteria, the possible function of the adaptor molecule IL-1R\u2013associated kinase (IRAK)-4 against this pathogen has not been addressed. In this study, we determined the role of IRAK-4 in signaling pathways responsible for controlling mycobacterial infections. This kinase is important for the production of IL-12 and TNF-\u03b1 by macrophages and dendritic cells exposed to mycobacteria. Moreover, Mycobacterium bovis\u2013infected IRAK-4\u2013knockout macrophages displayed impaired MAPK and NF-\u03baB activation. IL-1\u03b2 secretion and caspase-1 activation were also dependent on IRAK-4 signaling. Mice lacking IRAK-4 showed increased M. bovis burden in spleen, liver, and lungs and smaller liver granulomas during 60 d of infection compared with wild-type mice. Furthermore, 80% of IRAK-4\u2212\/\u2212 mice succumbed to virulent M. tuberculosis within 100 d following low-dose infection. This increased susceptibility to mycobacteria correlated with reduced IFN-\u03b3\/TNF-\u03b1 recall responses by splenocytes, as well as fewer IL-12p70\u2013producing APCs. Additionally, we observed that IRAK-4 is also important for the production of IFN-\u03b3 by CD4+ T cells from infected mice. Finally, THP-1 cells treated with an IRAK-4 inhibitor and exposed to M. bovis showed reduced TNF-\u03b1 and IL-12, suggesting that the results found in mice can be extended to humans. In summary, these data demonstrate that IRAK-4 is essential for innate and adaptive immunity and necessary for efficient control of mycobacterial infections.<\/jats:p>","DOI":"10.4049\/jimmunol.1502157","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T02:39:14Z","timestamp":1469068754000},"page":"1852-1863","source":"Crossref","is-referenced-by-count":12,"title":["Lack of IL-1 Receptor\u2013Associated Kinase-4 Leads to Defective Th1 Cell Responses and Renders Mice Susceptible to Mycobacterial Infection"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6885-3438","authenticated-orcid":false,"given":"F\u00e1bio V","family":"Marinho","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falia S","family":"Fahel","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-5603","authenticated-orcid":false,"given":"Charles A","family":"Scanga","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-1200","authenticated-orcid":false,"given":"Marco Tulio R","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle R M","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanny V","family":"Morales","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina , Florian\u00f3polis, Santa Catarina 88040900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5148-600X","authenticated-orcid":false,"given":"Andr\u00e9","family":"B\u00e1fica","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina , Florian\u00f3polis, Santa Catarina 88040900,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio Costa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"2025030617480124800_r1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.immunol.21.120601.141126","article-title":"Toll-like receptors","volume":"21","author":"Takeda","year":"2003","journal-title":"Annu. 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Pathol."},{"key":"2025030617480124800_r24","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1128\/IAI.72.4.2400-2404.2004","article-title":"MyD88-deficient mice display a profound loss in resistance to Mycobacterium tuberculosis associated with partially impaired Th1 cytokine and nitric oxide synthase 2 expression","volume":"72","author":"Scanga","year":"2004","journal-title":"Infect. Immun."},{"key":"2025030617480124800_r25","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.4049\/jimmunol.171.9.4758","article-title":"Mice lacking myeloid differentiation factor 88 display profound defects in host resistance and immune responses to Mycobacterium avium infection not exhibited by Toll-like receptor 2 (TLR2)- and TLR4-deficient animals","volume":"171","author":"Feng","year":"2003","journal-title":"J. Immunol."},{"key":"2025030617480124800_r26","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.4049\/jimmunol.169.7.3480","article-title":"Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis","volume":"169","author":"Reiling","year":"2002","journal-title":"J. Immunol."},{"key":"2025030617480124800_r27","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1084\/jem.178.6.2249","article-title":"An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection","volume":"178","author":"Flynn","year":"1993","journal-title":"J. Exp. Med."},{"key":"2025030617480124800_r28","first-page":"423","article-title":"The role of interleukin-12 in acquired immunity to Mycobacterium tuberculosis infection","volume":"84","author":"Cooper","year":"1995","journal-title":"Immunology"},{"key":"2025030617480124800_r29","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1086\/315466","article-title":"CD4+ and CD8+ T cells mediate adoptive immunity to aerosol infection of Mycobacterium bovis bacillus Calmette-Gu\u00e9rin","volume":"181","author":"Feng","year":"2000","journal-title":"J. Infect. Dis."},{"key":"2025030617480124800_r30","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/labinvest.3780094","article-title":"Correction of defective host response to Mycobacterium bovis BCG infection in TNF-deficient mice by bone marrow transplantation","volume":"80","author":"Jacobs","year":"2000","journal-title":"Lab. 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Immunol."},{"key":"2025030617480124800_r34","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.4049\/jimmunol.179.2.1178","article-title":"IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection","volume":"179","author":"Fremond","year":"2007","journal-title":"J. Immunol."},{"key":"2025030617480124800_r35","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.4049\/jimmunol.0904189","article-title":"Caspase-1 independent IL-1beta production is critical for host resistance to Mycobacterium tuberculosis and does not require TLR signaling in vivo","volume":"184","author":"Mayer-Barber","year":"2010","journal-title":"J. Immunol."},{"key":"2025030617480124800_r36","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/nature04926","article-title":"Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity","volume":"442","author":"Gross","year":"2006","journal-title":"Nature"},{"key":"2025030617480124800_r37","doi-asserted-by":"crossref","first-page":"5243","DOI":"10.1073\/pnas.94.10.5243","article-title":"Identification of nitric oxide synthase as a protective locus against tuberculosis","volume":"94","author":"MacMicking","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030617480124800_r38","doi-asserted-by":"crossref","first-page":"36560","DOI":"10.1074\/jbc.M506831200","article-title":"Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-kappaB activation but does not contribute to interferon regulatory factor 3 activation","volume":"280","author":"Cusson-Hermance","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025030617480124800_r39","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"key":"2025030617480124800_r40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00005-015-0365-7","article-title":"Type I, II, and III interferons: regulating immunity to Mycobacterium tuberculosis infection","volume":"64","author":"Travar","year":"2016","journal-title":"Arch. Immunol. Ther. Exp. (Warsz.)"},{"key":"2025030617480124800_r41","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/iid3.9","article-title":"Relative contribution of IL-1\u03b1, IL-1\u03b2 and TNF to the host response to Mycobacterium tuberculosis and attenuated M. bovis BCG","volume":"1","author":"Bourigault","year":"2013","journal-title":"Immun. Inflamm. Dis."},{"key":"2025030617480124800_r42","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.smim.2014.09.009","article-title":"The formation of the granuloma in tuberculosis infection","volume":"26","author":"Orme","year":"2014","journal-title":"Semin. Immunol."},{"key":"2025030617480124800_r43","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.micinf.2008.07.039","article-title":"Innate immunity in tuberculosis: myths and truth","volume":"10","author":"Korbel","year":"2008","journal-title":"Microbes Infect."},{"key":"2025030617480124800_r44","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/imr.12266","article-title":"Macrophage defense mechanisms against intracellular bacteria","volume":"264","author":"Weiss","year":"2015","journal-title":"Immunol. Rev."},{"key":"2025030617480124800_r45","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1189\/jlb.3A1114-557R","article-title":"Role for NOD2 in Mycobacterium tuberculosis-induced iNOS expression and NO production in human macrophages","volume":"97","author":"Landes","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"2025030617480124800_r46","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1128\/IAI.05289-11","article-title":"Interleukin-1 receptor-associated kinase 4 is essential for initial host control of Brucella abortus infection","volume":"79","author":"Oliveira","year":"2011","journal-title":"Infect. 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Invest."},{"key":"2025030617480124800_r49","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tube.2010.08.005","article-title":"The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis","volume":"90","author":"Krishnan","year":"2010","journal-title":"Tuberculosis (Edinb.)"},{"key":"2025030617480124800_r50","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1002\/eji.200425221","article-title":"Bacillus Calmette Guerin triggers the IL-12\/IFN-gamma axis by an IRAK-4- and NEMO-dependent, non-cognate interaction between monocytes, NK, and T lymphocytes","volume":"34","author":"Feinberg","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"2025030617480124800_r51","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1126\/science.1124256","article-title":"A critical role for the innate immune signaling molecule IRAK-4 in T cell activation","volume":"311","author":"Suzuki","year":"2006","journal-title":"Science"},{"key":"2025030617480124800_r52","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.jaci.2010.05.013","article-title":"Impaired T-cell receptor activation in IL-1 receptor-associated kinase-4-deficient patients","volume":"126","author":"McDonald","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025030617480124800_r53","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/imr.12285","article-title":"NLRP3 at the interface of metabolism and inflammation","volume":"265","author":"Haneklaus","year":"2015","journal-title":"Immunol. 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