{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T20:52:37Z","timestamp":1770324757460,"version":"3.49.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 112-2013-0100202"],"award-info":[{"award-number":["PIP 112-2013-0100202"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"National Agency for Scientific and Technological Promotion","doi-asserted-by":"publisher","award":["PICT 2015-0491"],"award-info":[{"award-number":["PICT 2015-0491"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008056","name":"Florencio Fiorini Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,13]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv. IL-22 and IL-17 expression and senescent status were assessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amount was measured in plasma and culture supernatants by enzyme-linked immunosorbent assay (ELISA). We found lower IL-22 amounts in plasma from TB patients than HD, together with a decrease in the number of circulating T cells expressing IL-22. In a similar manner, all Mtb strains enhanced IL-22 secretion and expanded IL-22+ cells within CD4+ and CD8+ subsets, being the highest levels detected in S-TB patients. In MDR-TB, low systemic and Mtb-induced Th22 responses associated with high sputum bacillary load and bilateralism of lung lesions, suggesting that Th22 response could be influencing the ability of MDR-TB patients to control bacillary growth and tissue damage. In addition, in MDR-TB patients we observed that the higher the percentage of IL-22+ cells, the lower the proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells. Furthermore, the highest proportion of senescent T cells was associated with severe lung lesions and bacillary load. Thus, T cell senescence would markedly influence Th22 response mounted by MDR-TB patients.<\/jats:p>","DOI":"10.1111\/cei.13544","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T16:41:43Z","timestamp":1604162503000},"page":"267-280","source":"Crossref","is-referenced-by-count":22,"title":["Th22 response induced by<i>Mycobacterium tuberculosis<\/i>strains is closely related to severity of pulmonary lesions and bacillary load in patients with multi-drug-resistant tuberculosis"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-8746","authenticated-orcid":false,"given":"B R","family":"Imperiale","sequence":"first","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Dr. F.J. Mu\u00f1iz Hospital, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Minotti","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Gonz\u00e1lez Montaner","sequence":"additional","affiliation":[{"name":"Dr. F.J. Mu\u00f1iz Hospital, Buenos Aires City, Argentina"},{"name":"Vaccareza Institute, UBA, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Moracho","sequence":"additional","affiliation":[{"name":"Dr. F.J. Mu\u00f1iz Hospital, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N S","family":"Morcillo","sequence":"additional","affiliation":[{"name":"Tuberculosis and Mycobacterioses Laboratory, Dr. Antonio A. Cetr\u00e1ngolo Hospital, Buenos Aires Province, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"Palmero","sequence":"additional","affiliation":[{"name":"Dr. F.J. Mu\u00f1iz Hospital, Buenos Aires City, Argentina"},{"name":"Vaccareza Institute, UBA, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"del Carmen Sasiain","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"de la Barrera","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"2021121023212239500_cei13544-bib-0001","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1146\/annurev-immunol-032414-112123","article-title":"Interleukin-22: immunobiology and pathology","volume":"33","author":"Dudakov","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"2021121023212239500_cei13544-bib-0002","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.cytogfr.2006.09.001","article-title":"Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the biology of tissue cells","volume":"17","author":"Wolk","year":"2006","journal-title":"Cytokine Growth Factor Rev"},{"key":"2021121023212239500_cei13544-bib-0003","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.3389\/fimmu.2018.02209","article-title":"IL-22: an underestimated player in natural resistance to tuberculosis?","volume":"9","author":"Ronacher","year":"2018","journal-title":"Front Immunol"},{"key":"2021121023212239500_cei13544-bib-0004","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4049\/immunohorizons.1800006","article-title":"IL-22: there is a gap in our knowledge","volume":"2","author":"Zenewicz","year":"2018","journal-title":"ImmunoHorizons"},{"key":"2021121023212239500_cei13544-bib-0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-381300-8.00001-0","article-title":"Functional biology of the IL-22-IL-22R pathway in regulating immunity and inflammation at barrier surfaces","volume":"107","author":"Sonnenberg","year":"2010","journal-title":"Adv Immunol"},{"key":"2021121023212239500_cei13544-bib-0006","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cytogfr.2012.07.002","article-title":"Emerging role of interleukin-22 in autoimmune diseases","volume":"24","author":"Pan","year":"2013","journal-title":"Cytokine Growth Factor Rev"},{"key":"2021121023212239500_cei13544-bib-0007","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/mi.2017.15","article-title":"Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection","volume":"10","author":"Treerat","year":"2017","journal-title":"Mucosal Immunol"},{"key":"2021121023212239500_cei13544-bib-0008","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4049\/jimmunol.1004129","article-title":"Membrane-bound IL-22 after de novo production in tuberculosis and anti- mycobacterium tuberculosis effector function of IL-22 + CD4+ T cells","volume":"187","author":"Zeng","year":"2011","journal-title":"J Immunol"},{"key":"2021121023212239500_cei13544-bib-0009","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/infdis\/jit495","article-title":"Interleukin 22 inhibits intracellular growth of mycobacterium tuberculosis by enhancing calgranulin a expression","volume":"209","author":"Dhiman","year":"2014","journal-title":"J Infect Dis"},{"key":"2021121023212239500_cei13544-bib-0010","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4049\/jimmunol.186.Supp.158.21","article-title":"IL-22 enhances Calgranulin A expression by human macrophages to inhibit virulent Mycobacterium tuberculosis growth","volume":"186","author":"Dhiman","year":"2011","journal-title":"J Immunol"},{"key":"2021121023212239500_cei13544-bib-0011","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.imlet.2012.12.008","article-title":"Depletion of IL-22 during culture enhanced antigen-driven IFN-\u03b3 production by CD4(+) T cells from patients with active TB","volume":"150","author":"Qiu","year":"2013","journal-title":"Immunol Lett"},{"key":"2021121023212239500_cei13544-bib-0012","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1128\/IAI.00282-13","article-title":"Low induction of proinflammatory cytokines parallels evolutionary success of modern strains within the Mycobacterium tuberculosis Beijing genotype","volume":"81","author":"van Laarhoven","year":"2013","journal-title":"Infect Immun"},{"key":"2021121023212239500_cei13544-bib-0013","author":"TUBERCULOSIS EN ARGENTINA-PRO.TB.TEC 28\/20 INER-ANLIS-MSAL"},{"key":"2021121023212239500_cei13544-bib-0014","first-page":"45","article-title":"Multidrug resistant tuberculosis outbreak in Buenos Aires. 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