{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:24:08Z","timestamp":1769581448419,"version":"3.49.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R01AI116438"],"award-info":[{"award-number":["R01AI116438"]}]},{"name":"Funda\u00e7\u00e3o de Apoia \u00e0 Pesquisa do Esp\u00edrito Santo","award":["50204076"],"award-info":[{"award-number":["50204076"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Regulatory T cells (Tregs) play a critical role during <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the <jats:italic>in vitro<\/jats:italic> microbicidal activity against <jats:italic>Mtb<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We evaluated the <jats:italic>in vitro<\/jats:italic> microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+\/IGRA+) and healthy control (HC, TST-\/IGRA-) volunteers. PBMCs, depleted or not of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T-cells, were analyzed to determine frequency and influence on microbicidal activity during <jats:italic>in vitro Mtb<\/jats:italic> infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The frequency of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> cells were significantly higher in <jats:italic>Mtb<\/jats:italic> infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> T-cells depletion demonstrate that increase of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>high<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> is associated with an impairment of Th-1 responses and a diminished <jats:italic>in vitro<\/jats:italic> microbicidal activity of LTBI and TB groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0009605","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T18:23:06Z","timestamp":1627582986000},"page":"e0009605","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8710-3648","authenticated-orcid":true,"given":"Lorenzzo Lyrio","family":"Stringari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-0137","authenticated-orcid":true,"given":"Luciana Polaco","family":"Covre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-2788","authenticated-orcid":true,"given":"Fl\u00e1via Dias Coelho","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2523-0374","authenticated-orcid":true,"given":"Vivian Leite","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carolina","family":"Campana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Jamil","family":"Hadad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mois\u00e9s","family":"Palaci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padmini","family":"Salgame","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6995-8001","authenticated-orcid":true,"given":"Reynaldo","family":"Dietze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-0981","authenticated-orcid":true,"given":"Daniel Cl\u00e1udio de Oliveira","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-110X","authenticated-orcid":true,"given":"Rodrigo","family":"Ribeiro-Rodrigues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"issue":"5","key":"pntd.0009605.ref001","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.4049\/jimmunol.178.5.2661","article-title":"Cutting Edge: Regulatory T cells prevent efficient clearance of Mycobacterium tuberculosis","volume":"178","author":"M Kursar","year":"2007","journal-title":"J Immunol"},{"key":"pntd.0009605.ref002","volume-title":"Latent tuberculosis infection: updated and consolidated guidelines for programmatic 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