{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:09:13Z","timestamp":1789178953438,"version":"build-2803163510"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T00:00:00Z","timestamp":1479340800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T00:00:00Z","timestamp":1479340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antibodies targeting IL-17A or its receptor IL-17RA show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. These therapies, by neutralizing critical mediators of immunity, may increase susceptibility to infections. Here, we compared the effect of antibodies neutralizing IL-17A, IL-17F or TNF\u03b1 on murine host responses to <jats:italic>Mycobacterium tuberculosis<\/jats:italic> infection by evaluating lung transcriptomic, microbiological and histological analyses. Coinciding with a significant increase of mycobacterial burden and pathological changes following TNF\u03b1 blockade, gene array analyses of infected lungs revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection. Specifically, gene expression associated with host-pathogen interactions, macrophage recruitment, activation and polarization, host-antimycobacterial activities, immunomodulatory responses, as well as extracellular matrix metallopeptidases, were markedly modulated by TNF\u03b1 blockade. IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after <jats:italic>M. tuberculosis<\/jats:italic> infection. Further, the absence of both IL-17RA and IL-22 pathways in genetically deficient mice did not profoundly compromise host control of <jats:italic>M. tuberculosis<\/jats:italic> over a 6-months period, ruling out potential compensation between these two pathways, while TNF\u03b1-deficient mice succumbed rapidly. These data provide experimental confirmation of the low clinical risk of mycobacterial infection under anti-IL-17A therapy, in contrast to anti-TNF\u03b1 treatment.<\/jats:p>","DOI":"10.1038\/srep36923","type":"journal-article","created":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T14:16:34Z","timestamp":1479392194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Controlled Mycobacterium tuberculosis infection in mice under treatment with anti-IL-17A or IL-17F antibodies, in contrast to TNF\u03b1 neutralization"],"prefix":"10.1038","volume":"6","author":[{"given":"Noria","family":"Segueni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Tritto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Bourigault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Erard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Le Bert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muazzam","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Di Padova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Stiehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Moulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Brees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah-Dine","family":"Chibout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Ryffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kamm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie F.","family":"Quesniaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,17]]},"reference":[{"key":"BFsrep36923_CR1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/BOR.0000000000000147","volume":"27","author":"PJ Mease","year":"2015","unstructured":"Mease, P. J. Inhibition of interleukin-17, interleukin-23 and the TH17 cell pathway in the treatment of psoriatic arthritis and psoriasis. Curr. Opin. Rheumatol. 27, 127\u2013133 (2015).","journal-title":"Curr. Opin. Rheumatol."},{"key":"BFsrep36923_CR2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1056\/NEJMoa1314258","volume":"371","author":"RG Langley","year":"2014","unstructured":"Langley, R. G. et al. Secukinumab in plaque psoriasis\u2013results of two phase 3 trials. N. Engl. J. Med. 371, 326\u2013338 (2014).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep36923_CR3","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1056\/NEJMoa1505066","volume":"373","author":"D Baeten","year":"2015","unstructured":"Baeten, D. et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N. Engl. J. Med. 373, 2534\u20132548 (2015).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep36923_CR4","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","volume":"14","author":"SL Gaffen","year":"2014","unstructured":"Gaffen, S. L., Jain, R., Garg, A. V. & Cua, D. J. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nature Rev. Immunol. 14, 585\u2013600 (2014).","journal-title":"Nature Rev. Immunol"},{"key":"BFsrep36923_CR5","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1002\/eji.201242605","volume":"42","author":"S Cypowyj","year":"2012","unstructured":"Cypowyj, S., Picard, C., Marodi, L., Casanova, J. L. & Puel, A. Immunity to infection in IL-17-deficient mice and humans. Eur. J. Immunol. 42, 2246\u20132254 (2012).","journal-title":"Eur. J. Immunol."},{"key":"BFsrep36923_CR6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2249.2010.04146.x","volume":"161","author":"J Harris","year":"2010","unstructured":"Harris, J. & Keane, J. How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin. Exp. Immunol. 161, 1\u20139 (2010).","journal-title":"Clin. Exp. Immunol"},{"key":"BFsrep36923_CR7","first-page":"47","volume":"91","author":"F Cantini","year":"2014","unstructured":"Cantini, F., Niccoli, L. & Goletti, D. Adalimumab, etanercept, infliximab, and the risk of tuberculosis: data from clinical trials, national registries, and postmarketing surveillance. J. Rheumatol. Supplement 91, 47\u201355 (2014).","journal-title":"J. Rheumatol."},{"key":"BFsrep36923_CR8","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.1128\/IAI.00621-06","volume":"74","author":"AA Chackerian","year":"2006","unstructured":"Chackerian, A. A. et al. Neutralization or absence of the interleukin-23 pathway does not compromise immunity to mycobacterial infection. Infect. Immunity 74, 6092\u20136099 (2006).","journal-title":"Infect. Immunity"},{"key":"BFsrep36923_CR9","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ni1449","volume":"8","author":"SA Khader","year":"2007","unstructured":"Khader, S. A. et al. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8, 369\u2013377 (2007).","journal-title":"Nat. Immunol."},{"key":"BFsrep36923_CR10","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.4049\/jimmunol.0903332","volume":"184","author":"Y Okamoto Yoshida","year":"2010","unstructured":"Okamoto Yoshida, Y. et al. Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J. Immunol. 184, 4414\u20134422 (2010).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/imm.12130","volume":"140","author":"D Freches","year":"2013","unstructured":"Freches, D. et al. Mice genetically inactivated in interleukin-17A receptor are defective in long-term control of Mycobacterium tuberculosis infection. Immunology 140, 220\u2013231 (2013).","journal-title":"Immunology"},{"key":"BFsrep36923_CR12","doi-asserted-by":"crossref","first-page":"e1004099","DOI":"10.1371\/journal.ppat.1004099","volume":"10","author":"R Gopal","year":"2014","unstructured":"Gopal, R. et al. Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection. PLoS Pathogens 10, e1004099 (2014).","journal-title":"PLoS Pathogens"},{"key":"BFsrep36923_CR13","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.cytogfr.2010.10.004","volume":"21","author":"E Torrado","year":"2010","unstructured":"Torrado, E. & Cooper, A. M. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 21, 455\u2013462 (2010).","journal-title":"Cytokine Growth Factor Rev"},{"key":"BFsrep36923_CR14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1189\/jlb.0809550","volume":"88","author":"FL van de Veerdonk","year":"2010","unstructured":"van de Veerdonk, F. L. et al. Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. J. Leukoc. Biol. 88, 227\u2013232 (2010).","journal-title":"J. Leukoc. Biol."},{"key":"BFsrep36923_CR15","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1128\/IAI.00282-13","volume":"81","author":"A van Laarhoven","year":"2013","unstructured":"van Laarhoven, A. et al. Low Induction of Proinflammatory Cytokines Parallels Evolutionary Success of Modern Strains within the Mycobacterium tuberculosis Beijing Genotype. Infect. Immunity 81, 3750\u20133756 (2013).","journal-title":"Infect. Immunity"},{"key":"BFsrep36923_CR16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/imr.12274","volume":"264","author":"LD Jasenosky","year":"2015","unstructured":"Jasenosky, L. D., Scriba, T. J., Hanekom, W. A. & Goldfeld, A. E. T cells and adaptive immunity to Mycobacterium tuberculosis in humans. Immunol. Rev. 264, 74\u201387 (2015).","journal-title":"Immunol. Rev."},{"key":"BFsrep36923_CR17","doi-asserted-by":"publisher","first-page":"e0149455","DOI":"10.1371\/journal.pone.0149455","volume":"11","author":"R Lombard","year":"2016","unstructured":"Lombard, R. et al. IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response. PLoS One 11, e0149455, doi: 10.1371\/journal.pone.0149455 (2016).","journal-title":"PLoS One"},{"key":"BFsrep36923_CR18","doi-asserted-by":"publisher","first-page":"e1003472","DOI":"10.1371\/journal.ppat.1003472","volume":"9","author":"L Kozakiewicz","year":"2013","unstructured":"Kozakiewicz, L. et al. B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response. PLoS Pathog 9, e1003472, doi: 10.1371\/journal.ppat.1003472 (2013).","journal-title":"PLoS Pathog"},{"key":"BFsrep36923_CR19","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.vaccine.2014.11.013","volume":"33","author":"A Cruz","year":"2015","unstructured":"Cruz, A. et al. BCG vaccination-induced long-lasting control of Mycobacterium tuberculosis correlates with the accumulation of a novel population of CD4+IL-17+TNF+IL-2+ T cells. Vaccine 33, 85\u201391 (2015).","journal-title":"Vaccine"},{"key":"BFsrep36923_CR20","doi-asserted-by":"publisher","first-page":"29990","DOI":"10.1038\/srep29990","volume":"6","author":"S Steinbach","year":"2016","unstructured":"Steinbach, S., Vordermeier, H. M. & Jones, G. J. CD4+ and \u03b3\u03b4 T Cells are the main Producers of IL-22 and IL-17A in Lymphocytes from Mycobacterium bovis-infected Cattle. Sci. Rep. 6, 29990, doi: 10.1038\/srep29990 (2016).","journal-title":"Sci. Rep."},{"key":"BFsrep36923_CR21","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1164\/rccm.201003-0334OC","volume":"182","author":"BMN Kagina","year":"2010","unstructured":"Kagina, B. M. N. et al. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Gu\u00e9rin vaccination of newborns. Am. J. Respir. Crit. Care Med. 182, 1073\u20131079 (2010).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFsrep36923_CR22","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1146\/annurev-pathol-011110-130318","volume":"8","author":"CT Weaver","year":"2013","unstructured":"Weaver, C. T., Elson, C. O., Fouser, L. A. & Kolls, J. K. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu. Rev. Pathol. 8, 477\u2013512 (2013).","journal-title":"Annu. Rev. Pathol."},{"key":"BFsrep36923_CR23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-immunol-032712-095939","volume":"31","author":"A O\u2019Garra","year":"2013","unstructured":"O\u2019Garra, A. et al. The immune response in tuberculosis. Annu. Rev. Immunol. 31, 475\u2013527 (2013).","journal-title":"Annu. Rev. Immunol."},{"key":"BFsrep36923_CR24","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.4049\/jimmunol.179.2.1178","volume":"179","author":"CM Fremond","year":"2007","unstructured":"Fremond, C. M. et al. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J. Immunol. 179, 1178\u20131189 (2007).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR25","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/1074-7613(95)90001-2","volume":"2","author":"JL Flynn","year":"1995","unstructured":"Flynn, J. L. et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561\u2013572 (1995).","journal-title":"Immunity"},{"key":"BFsrep36923_CR26","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1038\/srep01809","volume":"3","author":"N Allie","year":"2013","unstructured":"Allie, N. et al. Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection. Sci. Rep. 3, 1809 (2013).","journal-title":"Sci. Rep."},{"key":"BFsrep36923_CR27","doi-asserted-by":"crossref","first-page":"22454","DOI":"10.1038\/srep22454","volume":"6","author":"N Segueni","year":"2016","unstructured":"Segueni, N. et al. Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection. Sci. Rep. 6, 22454 (2016).","journal-title":"Sci. Rep"},{"key":"BFsrep36923_CR28","doi-asserted-by":"crossref","first-page":"6107","DOI":"10.4049\/jimmunol.165.11.6107","volume":"165","author":"C Infante-Duarte","year":"2000","unstructured":"Infante-Duarte, C., Horton, H. F., Byrne, M. C. & Kamradt, T. Microbial lipopeptides induce the production of IL-17 in Th cells. J. Immunol. 165, 6107\u20136115 (2000).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR29","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1189\/jlb.3RU0814-386R","volume":"97","author":"KO Busman-Sahay","year":"2015","unstructured":"Busman-Sahay, K. O., Walrath, T., Huber, S. & O\u2019Connor, W. Jr. Cytokine crowdsourcing: multicellular production of TH17-associated cytokines. J. Leukoc. Biol. 97, 499\u2013510 (2015).","journal-title":"J. Leukoc. Biol."},{"key":"BFsrep36923_CR30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/imr.12183","volume":"260","author":"JP McAleer","year":"2014","unstructured":"McAleer, J. P. & Kolls, J. K. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense. Immunol. Rev. 260, 129\u2013144 (2014).","journal-title":"Immunol. Rev."},{"key":"BFsrep36923_CR31","doi-asserted-by":"publisher","first-page":"e58966","DOI":"10.1371\/journal.pone.0058966","volume":"8","author":"AC Melton","year":"2013","unstructured":"Melton, A. C. et al. Regulation of IL-17A Production Is Distinct from IL-17F in a Primary Human Cell Co-culture Model of T Cell-Mediated B Cell Activation. PLoS One 8(3), e58966. doi: 10.1371\/journal.pone.0058966 (2013).","journal-title":"PLoS One"},{"key":"BFsrep36923_CR32","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1189\/jlb.4A0915-428R","volume":"99","author":"N Whibley","year":"2016","unstructured":"Whibley, N. et al. Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis. J. Leukoc. Biol. 99, 1153\u20131164 (2016).","journal-title":"J. Leukoc. Biol."},{"key":"BFsrep36923_CR33","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1002\/eji.201444891","volume":"44","author":"S Eyerich","year":"2014","unstructured":"Eyerich, S. & Zielinski, C. E. Defining Th-cell subsets in a classical and tissue-specific manner: Examples from the skin. Eur. J. Immunol. 44, 3475\u20133483 (2014).","journal-title":"Eur. J. Immunol."},{"key":"BFsrep36923_CR34","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.4049\/jimmunol.180.3.1962","volume":"180","author":"TJ Scriba","year":"2008","unstructured":"Scriba, T. J. et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J. Immunol. 180, 1962\u20131970 (2008).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tube.2011.06.009","volume":"91","author":"K Matthews","year":"2011","unstructured":"Matthews, K. et al. Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis. Tuberculosis (Edinb) 91, 587\u2013593 (2011).","journal-title":"Tuberculosis"},{"key":"BFsrep36923_CR36","doi-asserted-by":"crossref","first-page":"e57379","DOI":"10.1371\/journal.pone.0057379","volume":"8","author":"J Behrends","year":"2013","unstructured":"Behrends, J., Renauld, J. C., Ehlers, S. & Holscher, C. IL-22 is mainly produced by IFNgamma-secreting cells but is dispensable for host protection against Mycobacterium tuberculosis infection. PloS One 8, e57379 (2013).","journal-title":"PloS One"},{"key":"BFsrep36923_CR37","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.4049\/jimmunol.0903416","volume":"184","author":"MS Wilson","year":"2010","unstructured":"Wilson, M. S. et al. Redundant and pathogenic roles of IL-22 in mycobacterial, protozoan, and helminth infections. J. Immunol. 184, 4378\u20134390 (2010).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR38","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1126\/science.aaa4282","volume":"349","author":"S Okada","year":"2015","unstructured":"Okada, S. et al. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349, 606\u2013613 (2015).","journal-title":"Science"},{"key":"BFsrep36923_CR39","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1002\/eji.201040433","volume":"40","author":"PS Redford","year":"2010","unstructured":"Redford, P. S. et al. Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung. Eur. J. Immunol. 40, 2200\u20132210 (2010).","journal-title":"Eur. J. Immunol."},{"key":"BFsrep36923_CR40","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.immuni.2010.06.001","volume":"32","author":"HJ Wu","year":"2010","unstructured":"Wu, H. J. et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32, 815\u2013827 (2010).","journal-title":"Immunity"},{"key":"BFsrep36923_CR41","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1086\/517519","volume":"195","author":"HL Plessner","year":"2007","unstructured":"Plessner, H. L. et al. Neutralization of tumor necrosis factor (TNF) by antibody but not TNF receptor fusion molecule exacerbates chronic murine tuberculosis. J. Infect. Dis. 195, 1643\u20131650 (2007).","journal-title":"J. Infect. Dis."},{"key":"BFsrep36923_CR42","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1002\/art.22750","volume":"56","author":"CL Bigbee","year":"2007","unstructured":"Bigbee, C. L. et al. Abatacept treatment does not exacerbate chronic Mycobacterium tuberculosis infection in mice. Arthritis Rheumatol. 56, 2557\u20132565 (2007).","journal-title":"Arthritis Rheumatol."},{"key":"BFsrep36923_CR43","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1165\/rcmb.2008-0248OC","volume":"40","author":"M Gonzalez-Juarrero","year":"2009","unstructured":"Gonzalez-Juarrero, M. et al. Immune response to Mycobacterium tuberculosis and identification of molecular markers of disease. Am. J. Resp. Cell Mol. Biol. 40, 398\u2013409 (2009).","journal-title":"Am. J. Resp. Cell Mol. Biol."},{"key":"BFsrep36923_CR44","doi-asserted-by":"crossref","first-page":"e16161","DOI":"10.1371\/journal.pone.0016161","volume":"6","author":"DD Kang","year":"2011","unstructured":"Kang, D. D., Lin, Y., Moreno, J. R., Randall, T. D. & Khader, S. A. Profiling early lung immune responses in the mouse model of tuberculosis. PLoS One 6, e16161 (2011).","journal-title":"PLoS One"},{"key":"BFsrep36923_CR45","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00281-015-0531-3","volume":"38","author":"A Dorhoi","year":"2016","unstructured":"Dorhoi, A. & Kaufmann, S. H. E. Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis. Semin. Immunopathol. 38, 153\u2013166 (2016).","journal-title":"Semin. Immunopathol."},{"key":"BFsrep36923_CR46","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1128\/IAI.02494-14","volume":"83","author":"S Marino","year":"2015","unstructured":"Marino, S. et al. Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection. Infect. Immunity 83, 324\u2013338 (2015).","journal-title":"Infect. Immunity"},{"key":"BFsrep36923_CR47","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.smim.2014.09.010","volume":"26","author":"MV Rajaram","year":"2014","unstructured":"Rajaram, M. V., Ni, B., Dodd, C. E. & Schlesinger, L. S. Macrophage immunoregulatory pathways in tuberculosis. Semin. Immunol. 26, 471\u2013485 (2014).","journal-title":"Semin. Immunol."},{"key":"BFsrep36923_CR48","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/eji.201545493","volume":"45","author":"A Dorhoi","year":"2015","unstructured":"Dorhoi, A. & Kaufmann, S. H. E. Versatile myeloid cell subsets contribute to tuberculosis-associated inflammation. Eur. J. Immunol. 45, 2191\u20132202 (2015).","journal-title":"Eur. J. Immunol."},{"key":"BFsrep36923_CR49","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1164\/rccm.201405-0828OC","volume":"190","author":"JK Knaul","year":"2014","unstructured":"Knaul, J. K. et al. Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 190, 1053\u20131066 (2014).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFsrep36923_CR50","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.immuni.2013.02.007","volume":"38","author":"M Sade-Feldman","year":"2013","unstructured":"Sade-Feldman, M. et al. Tumor necrosis factor-alpha blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation. Immunity 38, 541\u2013554 (2013).","journal-title":"Immunity"},{"key":"BFsrep36923_CR51","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1164\/rccm.201304-0803OC","volume":"188","author":"R Gopal","year":"2013","unstructured":"Gopal, R. et al. S100A8\/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. Am. J. Respir. Crit. Care Med. 188, 1137\u20131146 (2013).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFsrep36923_CR52","doi-asserted-by":"crossref","first-page":"7820","DOI":"10.1073\/pnas.1218599110","volume":"110","author":"A Michelucci","year":"2013","unstructured":"Michelucci, A. et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl. Acad. Sci. 110, 7820\u20137825 (2013).","journal-title":"Proc. Natl. Acad. Sci"},{"key":"BFsrep36923_CR53","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s10495-014-1080-2","volume":"20","author":"Y-J Lim","year":"2015","unstructured":"Lim, Y.-J. et al. Mycobacterium tuberculosis 38-kDa antigen induces endoplasmic reticulum stress-mediated apoptosis vial toll-like receptor 2\/4. Apoptosis 20, 358\u2013370 (2015).","journal-title":"Apoptosis"},{"key":"BFsrep36923_CR54","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/j.ajpath.2014.03.008","volume":"184","author":"NK Dutta","year":"2014","unstructured":"Dutta, N. K., Illei, P. B., Jain, S. K. & Karakousis, P. C. Characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice. Am. J. Pathol. 184, 2045\u20132055 (2014).","journal-title":"Am. J. Pathol."},{"key":"BFsrep36923_CR55","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1164\/rccm.201311-2106PP","volume":"190","author":"CWM Ong","year":"2014","unstructured":"Ong, C. W. M., Elkington, P. T. & Friedland, J. S. Tuberculosis, Pulmonary Cavitation, and Matrix Metalloproteinases. Am. J. Respir. Crit. Care Med. 190, 9\u201318 (2014).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"BFsrep36923_CR56","doi-asserted-by":"crossref","first-page":"3110","DOI":"10.4049\/jimmunol.171.6.3110","volume":"171","author":"T Botha","year":"2003","unstructured":"Botha, T. & Ryffel, B. Reactivation of Latent Tuberculosis Infection in TNF-Deficient Mice. J. Immunol. 171, 3110\u20133118 (2003).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR57","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.4049\/jimmunol.177.3.1416","volume":"177","author":"A Cruz","year":"2006","unstructured":"Cruz, A. et al. Cutting edge: IFN-\u03b3 regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. J. Immunol. 177, 1416\u20131420 (2006).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR58","doi-asserted-by":"crossref","first-page":"4662","DOI":"10.4049\/jimmunol.177.7.4662","volume":"177","author":"E Lockhart","year":"2006","unstructured":"Lockhart, E., Green, A. M. & Flynn, J. L. IL-17 production is dominated by \u03b3\u03b4 T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol. 177, 4662\u20134669 (2006).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR59","doi-asserted-by":"crossref","first-page":"865","DOI":"10.4049\/jimmunol.0804080","volume":"183","author":"S von Vietinghoff","year":"2009","unstructured":"von Vietinghoff, S. & Ley, K. IL-17A controls IL-17F production and maintains blood neutrophil counts in mice. J. Immunol. 183, 865\u20131873 (2009).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR60","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ni.3048","volume":"16","author":"IM Orme","year":"2015","unstructured":"Orme, I. M., Robinson, R. T. & Cooper, A. M. The balance between protective and pathogenic immune repsonses in the TB-infected lung. Nat. Immunol. 16, 57\u201363 (2015).","journal-title":"Nat. Immunol."},{"key":"BFsrep36923_CR61","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1172\/JCI45005","volume":"124","author":"R Keeton","year":"2014","unstructured":"Keeton, R. et al. Soluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis. J. Clin. Invest. 124, 1537\u20131551 (2014).","journal-title":"J. Clin. Invest."},{"key":"BFsrep36923_CR62","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.4049\/jimmunol.1402797","volume":"194","author":"N Kapoor","year":"2015","unstructured":"Kapoor, N. et al. Transcription Factors STAT6 and KLF4 Implement Macrophage Polarization via the Dual Catalytic Powers of MCPIP. J. Immunol. 194, 6011\u20136023 (2015).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR63","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.immuni.2015.07.021","volume":"43","author":"AV Garg","year":"2015","unstructured":"Garg, A. V. et al. MCPIP1 Endoribonuclease Activity Negatively Regulates Interleukin-17-Mediated Signaling and Inflammation. Immunity 43, 475\u2013487 (2015).","journal-title":"Immunity"},{"key":"BFsrep36923_CR64","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.smim.2014.04.003","volume":"26","author":"A Dorhoi","year":"2014","unstructured":"Dorhoi, A. & Kaufmann, S. H. E. Tumor necrosis factor alpha in mycobacterial infection. Semin. Immunol. 26, 203\u2013209 (2014).","journal-title":"Semin. Immunol."},{"key":"BFsrep36923_CR65","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cell.2013.03.022","volume":"153","author":"FJ Roca","year":"2013","unstructured":"Roca, F. J. & Ramakrishnan, L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxigen species. Cell 153, 521\u2013534 (2013).","journal-title":"Cell"},{"key":"BFsrep36923_CR66","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/mi.2011.3","volume":"4","author":"SM Behar","year":"2011","unstructured":"Behar, S. M. et al. Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol. 4, 279\u2013287 (2011).","journal-title":"Mucosal Immunol"},{"key":"BFsrep36923_CR67","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tim.2014.01.005","volume":"22","author":"H Sridharan","year":"2014","unstructured":"Sridharan, H. & Upton, J. W. Programmed necrosis in microbial pathogenesis. Trends Microbiol. 22, 199\u2013207 (2014).","journal-title":"Trends Microbiol"},{"key":"BFsrep36923_CR68","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3389\/fimmu.2015.00498","volume":"6","author":"A Cruz","year":"2015","unstructured":"Cruz, A. et al. IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis of infected macrophages. Front. Immunol. 6, 498 (2015).","journal-title":"Front. Immunol"},{"key":"BFsrep36923_CR69","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.4049\/jimmunol.181.2.1357","volume":"181","author":"E Smith","year":"2008","unstructured":"Smith, E. et al. IL-17A inhibits the expansion of IL-17A-producing T cells in mice through \u201cshort-loop\u201d inhibition via IL-17 receptor. J. Immunol. 181, 1357\u20131364 (2008).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR70","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nm1710","volume":"14","author":"SJ Aujla","year":"2008","unstructured":"Aujla S. J. et al. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nature Med. 14, 275\u2013281 (2008).","journal-title":"Nature Med"},{"key":"BFsrep36923_CR71","unstructured":"Tsai, T. F., Blauvelt, A., Gong, Y., Huang, J. & Fox, T. Secukinumab Treatment Shows No Evidence for Reactivation of Previous or Latent TB Infection in Subjects with Psoriasis: A Pooled Phase 3 Safety Analysis [Abstract]. Am. Acad. Dermatology, Abstract 607 (2015)."},{"key":"BFsrep36923_CR72","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.194.4.519","volume":"194","author":"P Ye","year":"2001","unstructured":"Ye, P. et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194, 519\u2013527 (2001).","journal-title":"J. Exp. Med."},{"key":"BFsrep36923_CR73","doi-asserted-by":"crossref","first-page":"8098","DOI":"10.4049\/jimmunol.179.12.8098","volume":"179","author":"K Kreymborg","year":"2007","unstructured":"Kreymborg, K. et al. IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. J. Immunol. 179, 8098\u20138104 (2007).","journal-title":"J. Immunol."},{"key":"BFsrep36923_CR74","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1073\/pnas.94.15.8093","volume":"94","author":"MW Marino","year":"1997","unstructured":"Marino, M. W. et al. Characterization of tumor necrosis factor-deficient mice. Proc. Natl. Acad. Sci. 94, 8093\u20138098 (1997).","journal-title":"Proc. Natl. Acad. Sci"},{"key":"BFsrep36923_CR75","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1172\/JCI200421027","volume":"114","author":"CM Fremond","year":"2004","unstructured":"Fremond, C. M. et al. Fatal Mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. J Clin Invest 114, 1790\u20131799 (2004).","journal-title":"J Clin Invest"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36923.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36923","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36923.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:42:37Z","timestamp":1672886557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,17]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep36923"],"URL":"https:\/\/doi.org\/10.1038\/srep36923","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,17]]},"assertion":[{"value":"1 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36923"}}