{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:56:40Z","timestamp":1790985400354,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011781","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000}}],"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012309","name":"Royal Golden Jubilee (RGJ) Ph.D. Programme","doi-asserted-by":"publisher","award":["PHD\/0140\/2559"],"award-info":[{"award-number":["PHD\/0140\/2559"]}],"id":[{"id":"10.13039\/501100012309","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002873","name":"Chulalongkorn University","doi-asserted-by":"publisher","award":["the 90th Anniversary of Chulalongkorn University Fund"],"award-info":[{"award-number":["the 90th Anniversary of Chulalongkorn University Fund"]}],"id":[{"id":"10.13039\/501100002873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004776","name":"Faculty of Medicine, Chulalongkorn University","doi-asserted-by":"publisher","award":["Ratchadapiseksompotch Fund (RA65\/015)"],"award-info":[{"award-number":["Ratchadapiseksompotch Fund (RA65\/015)"]}],"id":[{"id":"10.13039\/501100004776","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Leptospirosis is a global zoonosis caused by pathogenic <jats:italic>Leptospira<\/jats:italic>. The disease outcome is influenced by the interplay between innate and adaptive immune responses. Dendritic cells (DCs) play a crucial role in shaping the adaptive immune response. A recent study revealed that pathogenic <jats:italic>Leptospira<\/jats:italic> limited the activation of human monocyte-derived dendritic cells (MoDCs) compared to non-pathogenic <jats:italic>Leptospira<\/jats:italic>, but their impact on T-cell responses has not been investigated. Our study is the first to explore how viable pathogenic and non-pathogenic <jats:italic>Leptospira<\/jats:italic> affect the interaction between human MoDCs and T cells. We found that MoDCs infected with pathogenic leptospires (<jats:italic>L<\/jats:italic>. <jats:italic>interrogans<\/jats:italic> serovar Pomona and a clinical isolate, MoDCs-P) exhibited lower levels of CD80 and CD83 expression, suggesting partially impaired MoDC maturation, induced regulatory T cells (Tregs) while failing to induce CD4<jats:sup>+<\/jats:sup> T cell proliferation, compared to MoDCs infected with non-pathogenic leptospires (<jats:italic>L<\/jats:italic>. <jats:italic>biflexa<\/jats:italic> serovar Patoc and <jats:italic>L<\/jats:italic>. <jats:italic>meyeri<\/jats:italic> serovar Ranarum, MoDCs-NP). In contrast, non-pathogenic leptospires enhanced MoDC maturation and induced higher T cell proliferation including IFN-\u03b3-producing CD4<jats:sup>+<\/jats:sup> T cells, indicative of a Th1-type response. Furthermore, pathogenic leptospires induced higher MoDC apoptosis through a cysteine aspartic acid-specific protease-3 (caspase-3)-dependent pathway and upregulated expression of the prostaglandin-endoperoxide synthase 2 (<jats:italic>PTGS2<\/jats:italic>) gene. Notably, prostaglandin E2 (PGE2), a product of the PTGS2 pathway, was found at higher levels in the sera of patients with acute leptospirosis and in the supernatant of MoDCs-P, possibly contributing to Treg induction, compared to those of healthy donors and MoDCs-NP, respectively. In conclusion, this study reveals a novel immunosuppressive strategy employed by pathogenic <jats:italic>Leptospira<\/jats:italic> to evade host immunity by partially impairing MoDC maturation and inducing Tregs. These findings deepen our understanding of leptospirosis pathogenesis in humans and may provide a novel strategy to modulate DCs for the prevention and treatment of the disease.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011781","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T18:44:31Z","timestamp":1700505871000},"page":"e0011781","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impaired functions of human monocyte-derived dendritic cells and induction of regulatory T cells by pathogenic 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