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The disease can lead to hepatic, renal, and pulmonary dysfunctions and may contribute to the development of chronic kidney disease. The Complement System plays an important role in eliminating bacteria by lysis, generating opsonins and anaphylatoxins, which degranulate mastocytes and basophils, and attracting immune cells to the site of infection, among other important functions. We aimed to investigate the role of C3 during chronic infection by\n                      <jats:italic toggle=\"yes\">L. interrogans<\/jats:italic>\n                      strain FIOCRUZ L1-130 (LIC) in C57BL\/6 wild-type (WT) and C3 knockout (C3KO) mice, monitored for 15, 30, 60, 90, or 180 days post-infection (d.p.i.). LIC-infected C3KO mice exhibited significantly higher leptospiral loads in the kidneys compared to WT counterparts. While both groups showed local inflammation at 15 and 30 d.p.i., LIC-infected C3KO showed a higher number of\n                      <jats:italic toggle=\"yes\">Leptospira<\/jats:italic>\n                      DNA copies at 30 d.p.i. At this same time point, C3KO LIC-infected mice developed a larger fibrotic area than WT mice. Additionally, levels of specific IgG2b and IgG3 antibodies were significantly higher in LIC-infected C3KO mice compared to WT mice. The number of na\u00efve T lymphocytes (both CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      ) was also increased in LIC-infected C3KO mice. This study demonstrates that during LIC infection, the absence of C3 does not impact mouse survival but results in increased renal leptospiral load and fibrosis. It also highlights the role of C3 in promoting the maturation and differentiation of T lymphocytes into pre-effector cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00398-25","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T13:00:15Z","timestamp":1763470815000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Complement C3 deficiency enhances renal leptospiral load and inflammation while impairing T cell differentiation during chronic\n                    <i>Leptospira interrogans<\/i>\n                    infection"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4231-2830","authenticated-orcid":true,"given":"Leonardo","family":"Moura Midon","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaro Nunes","family":"Duarte Neto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Faculty of Medicine, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Maria Gon\u00e7alves da Silva","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Tropical Medicine Institute, Faculty of Medicine, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Bryan Heinemann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Bacterial Zoonosis Laboratory, Medicine Veterinary School, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8591-1166","authenticated-orcid":true,"given":"Suman","family":"Kundu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-4543","authenticated-orcid":true,"given":"Maria","family":"Gomes-Solecki","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-8942","authenticated-orcid":true,"given":"Lourdes","family":"Isaac","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003898"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.23.3.377"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.2.296-326.2001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.03.012"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2008.07.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007499"},{"key":"e_1_3_3_8_2","first-page":"209","volume-title":"Deutsches Archiv f\u00fcr Klinische Medizin","author":"Weil A","year":"1886","unstructured":"Weil A. 1886. \u00dcber eine eigenth\u00fcmliche, mit Milztumor, Icterus und Nephritis einhergehende, acute Infektionskrankheit, p 209\u2013232. 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