{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:15:36Z","timestamp":1792080936627,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012527","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_184751"],"award-info":[{"award-number":["310030_184751"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_184751\/2"],"award-info":[{"award-number":["310030_184751\/2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_192523"],"award-info":[{"award-number":["310030_192523"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["INDO\/FRC\/452\/Y-32\/2022-23-IH & HRD"],"award-info":[{"award-number":["INDO\/FRC\/452\/Y-32\/2022-23-IH & HRD"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Intracellular pathogens that replicate in host myeloid cells have devised ways to inhibit the cell\u2019s killing machinery. Pyroptosis is one of the host strategies used to reduce the pathogen replicating niche and thereby control its expansion. The intracellular <jats:italic>Leishmania<\/jats:italic> parasites can survive and use neutrophils as a silent entry niche, favoring subsequent parasite dissemination into the host. Here, we show that <jats:italic>Leishmania mexicana<\/jats:italic> induces NLRP1- and caspase-1-dependent Gasdermin D (GSDMD)-mediated pyroptosis in neutrophils, a process critical to control the parasite-induced pathology. In the absence of GSDMD, we observe an increased number of infected dermal neutrophils two days post-infection. Using adoptive neutrophil transfer in neutropenic mice, we show that pyroptosis contributes to the regulation of the neutrophil niche early after infection. The critical role of neutrophil pyroptosis and its positive influence on the regulation of the disease outcome was further demonstrated following infection of mice with neutrophil-specific deletion of GSDMD. Thus, our study establishes neutrophil pyroptosis as a critical regulator of leishmaniasis pathology.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012527","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T17:30:34Z","timestamp":1725903034000},"page":"e1012527","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis"],"prefix":"10.1371","volume":"20","author":[{"given":"Michiel","family":"Goris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiuska","family":"Passelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanam","family":"Peyvandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"D\u00edaz-Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oaklyne","family":"Billion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Prat-Luri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Demarco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Desponds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Termote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Iniguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somaditya","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaden","family":"Kamhawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P.","family":"Hurrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Broz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3561-0207","authenticated-orcid":true,"given":"Fabienne","family":"Tacchini-Cottier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"issue":"2","key":"ppat.1012527.ref001","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"F Martinon","year":"2002","journal-title":"Mol 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Shi","year":"2015","journal-title":"Nature"},{"issue":"7575","key":"ppat.1012527.ref005","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"N Kayagaki","year":"2015","journal-title":"Nature"},{"issue":"10","key":"ppat.1012527.ref006","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1002\/eji.201545772","article-title":"Caspase-11 activates a canonical NLRP3 inflammasome by promoting K(+) efflux.","volume":"45","author":"S R\u00fchl","year":"2015","journal-title":"Eur J Immunol"},{"issue":"7610","key":"ppat.1012527.ref007","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nature18629","article-title":"Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores","volume":"535","author":"X Liu","year":"2016","journal-title":"Nature"},{"issue":"2","key":"ppat.1012527.ref008","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: host cell death and inflammation","volume":"7","author":"T Bergsbaken","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1012527.ref009","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1038\/s41467-020-16043-9","article-title":"N-GSDMD trafficking to neutrophil organelles facilitates IL-1\u03b2 release independently of plasma membrane pores and pyroptosis.","volume":"11","author":"M Karmakar","year":"2020","journal-title":"Nat Commun"},{"issue":"26","key":"ppat.1012527.ref010","article-title":"Noncanonical inflammasome signaling elicits gasdermin D\u2013dependent neutrophil extracellular traps","volume":"3","author":"KW Chen","year":"2018","journal-title":"Science 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Hickey","year":"2009","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"ppat.1012527.ref029","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.4049\/jimmunol.1000893","article-title":"Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil extracellular traps","volume":"185","author":"C Gabriel","year":"2010","journal-title":"J Immunol"},{"issue":"16","key":"ppat.1012527.ref030","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.1073\/pnas.0900226106","article-title":"Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps","volume":"106","author":"AB Guimar\u00e3es-Costa","year":"2009","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1012527.ref031","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.3389\/fimmu.2017.01558","article-title":"Survival Mechanisms Used by Some Leishmania Species to Escape Neutrophil Killing.","volume":"8","author":"IB Regli","year":"2017","journal-title":"Front Immunol."},{"key":"ppat.1012527.ref032","first-page":"12","article-title":"The Impact of Neutrophil Recruitment to the Skin on the Pathology Induced by Leishmania Infection.","author":"K Passelli","year":"2021","journal-title":"Frontiers in Immunology"},{"issue":"11","key":"ppat.1012527.ref033","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.4049\/jimmunol.173.11.6521","article-title":"Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into macrophages","volume":"173","author":"G van Zandbergen","year":"2004","journal-title":"J Immunol"},{"issue":"11","key":"ppat.1012527.ref034","doi-asserted-by":"crossref","first-page":"e1008674","DOI":"10.1371\/journal.ppat.1008674","article-title":"The role of dermis resident macrophages and their interaction with neutrophils in the early establishment of Leishmania major infection transmitted by sand fly bite.","volume":"16","author":"MM 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Kropf","year":"2004","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1012527.ref053","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1002\/eji.200737182","article-title":"TLR9 signaling is essential for the innate NK cell response in murine cutaneous leishmaniasis","volume":"37","author":"J Liese","year":"2007","journal-title":"Eur J Immunol"},{"issue":"6","key":"ppat.1012527.ref054","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.4049\/jimmunol.179.6.3988","article-title":"Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase","volume":"179","author":"FL Ribeiro-Gomes","year":"2007","journal-title":"J Immunol"},{"issue":"6","key":"ppat.1012527.ref055","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.jid.2018.12.012","article-title":"TLR2 Signaling in Skin Nonhematopoietic Cells Induces Early Neutrophil Recruitment in Response to Leishmania major 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