{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:57:05Z","timestamp":1790985425458,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI142129, R43 AI136551, R43 AI155211"],"award-info":[{"award-number":["R21 AI142129, R43 AI136551, R43 AI155211"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The exact global impact of leptospirosis is unknown due to inadequate surveillance systems in place in most low-income countries. In this study, we analyzed the differences in mouse inflammatory signatures involved in pathogenic versus non-pathogenic Leptospira recognition at 24h and 72h post infection. Injection of C3H-HeJ mice with non-pathogenic <jats:italic>L. biflexa<\/jats:italic> increased circulation of a few chemokines (5\/21, 24%) without secretion of cytokines in blood that resulted in engagement of resident macrophages, dendritic cells, neutrophils and NK cells without engagement of T cells. In contrast, pathogenic <jats:italic>L. interrogans<\/jats:italic> induced circulation of a much higher panel of chemokines (18\/21, 86%) and pro- and anti-inflammatory cytokines (11\/19, 58%) in blood with a resulting signaling cascade leading to engagement of macrophages, dendritic cells, monocytes, NK cells and T cells without engagement of neutrophils. Although neutrophils do not appear to be engaged, a considerable number of chemokines that recruit other granulocytes such as eosinophils and basophils were also increased at 72h post infection with <jats:italic>L. interrogans<\/jats:italic>. Overall, the data suggest that prevention of dissemination of <jats:italic>L. biflexa<\/jats:italic> is associated with an early engagement of the innate immune response characterized by upregulation of a few chemokines that results in an efficacious phagocytic response without an overwhelming increase of pro-inflammatory cytokines. However, when macrophages fail to clear a pathogenic serovar such as <jats:italic>L. interrogans<\/jats:italic>, the adaptive response (T cells) is engaged to help out, but the resulting chemo-cytokine storm mediates a robust but non-resolving inflammatory response to pathogenic Leptospira that results in dissemination, kidney colonization, pathology and disease.<\/jats:p>","DOI":"10.3389\/fcimb.2021.677999","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T08:12:37Z","timestamp":1624522357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Inflammatory Signatures of Pathogenic and Non-Pathogenic Leptospira Infection in Susceptible C3H-HeJ Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Advait","family":"Shetty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gomes-Solecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1128\/IAI.14.3.703-708.1976","article-title":"Susceptibility of Mice Treated With Cyclophosphamide to Lethal Infection With Leptospira Interrogans Serovar Pomona","volume":"14","author":"Adler","year":"1976","journal-title":"Infect. 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