{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:09:22Z","timestamp":1768568962762,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"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":["AI142129, AI155211"],"award-info":[{"award-number":["AI142129, AI155211"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to <jats:italic>Leptospira<\/jats:italic>. Groups of male C3H\/HeJ mice were infected with pathogenic <jats:italic>L. interrogans<\/jats:italic> and non-pathogenic <jats:italic>L. biflexa<\/jats:italic> for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic <jats:italic>L. interrogans<\/jats:italic> promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas <jats:italic>L. biflexa<\/jats:italic> promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with <jats:italic>L. interrogans<\/jats:italic> (neutrophils) and <jats:italic>L. biflexa<\/jats:italic> (monocytes) in our previous study. The same trend was observed with pathogenic <jats:italic>L. interrogans<\/jats:italic> inducing necroptosis of myeloid neutrophils in addition to monocytes and macrophages at 24h and\/or 72h post-infection, whereas <jats:italic>L. biflexa<\/jats:italic> promoted this pro-inflammatory cell death process in monocytes and macrophages only at 24h post-infection. Thus, early apoptosis and necroptosis of these cell types may explain its absence in frequency in spleen. Furthermore, at 24h and 72h, expression of the necroptosis molecular biomarkers p-MLKL, p-RIP1 and p-RIP3 was increased post infection with pathogenic <jats:italic>L. interrogans<\/jats:italic>. These data suggest that the underlying cell death processes involved in immune responses to pathogenic <jats:italic>Leptospira<\/jats:italic> contribute directly to persistent inflammation during the early stages of leptospirosis.<\/jats:p>","DOI":"10.3389\/fimmu.2022.810834","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T15:56:29Z","timestamp":1648482989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Suman","family":"Kundu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Advait","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Gomes-Solecki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.571816","article-title":"Phagocyte Escape of Leptospira: The Role of TLRs and NLRs","volume":"11","author":"Santecchia","year":"2020","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.677999","article-title":"Inflammatory Signatures of Pathogenic and Non-Pathogenic Leptospira Infection in Susceptible C3H-HeJ Mice","volume":"11","author":"Shetty","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/978-3-662-45059-8_5","article-title":"Leptospirosis in Humans","volume":"387","author":"Haake","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.3390\/cells10071585","article-title":"Cell Death in Coronavirus Infections: Uncovering Its Role During COVID-19","volume":"10","author":"Paolini","year":"2021","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00814","article-title":"Competitive Cell Death Interactions in Pulmonary Infection: Host Modulation Versus Pathogen Manipulation","volume":"11","author":"FitzGerald","year":"2020","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.91","article-title":"Cell Death in the Host Response to Infection","volume":"15","author":"Labb\u00e9","year":"2008","journal-title":"Cell Death Differentiation"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0270-8","article-title":"Emerging Connectivity of Programmed Cell Death Pathways and its Physiological Implications","volume":"21","author":"Bedoui","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0164-5","article-title":"The Molecular Machinery of Regulated Cell Death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.024","article-title":"The Coming Decade of Cell Death Research: Five Riddles","volume":"177","author":"Green","year":"2019","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.molimm.2020.11.001","article-title":"Enhanced RIPK3 Kinase Activity-Dependent Lytic Cell Death in M1 But Not M2 Macrophages","volume":"129","author":"Hao","year":"2021","journal-title":"Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41419-019-1490-8","article-title":"RIPK1 can Mediate Apoptosis in Addition to Necroptosis During Embryonic Development","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.003","article-title":"Necroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance","volume":"38","author":"Kaczmarek","year":"2013","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-0526-z","article-title":"Paradise Revealed III: Why So Many Ways to Die? 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