{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:53:27Z","timestamp":1778943207788,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010247","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"schweizerischer nationalfonds zur f\u00f6rderung der wissenschaftlichen forschung","doi-asserted-by":"publisher","award":["310030_184751\/1"],"award-info":[{"award-number":["310030_184751\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Neutrophils are the first line of defence against invading pathogens. Although neutrophils are well-known professional killers, some pathogens including <jats:italic>Leishmania (L<\/jats:italic>.<jats:italic>) parasites<\/jats:italic> survive in neutrophils, using these cells to establish infection. Manipulation of neutrophil recruitment to the infection site is therefore of interest in this cutaneous disease. The c-MET tyrosine kinase receptor was shown to promote neutrophil migration to inflamed sites. Here, we investigated the importance of c-MET expression on neutrophils in their recruitment to the infection site and the role of c-Met expression in the pathology of leishmaniasis. Following infection with <jats:italic>L<\/jats:italic>. <jats:italic>mexicana<\/jats:italic>, mice with conditional deletion of c-MET in neutrophils controlled significantly better their lesion development and parasite burden compared to similarly infected wild type mice. Our data reveal a specific role for c-MET activation in <jats:italic>Leishmania<\/jats:italic>-induced neutrophil infiltration, a process correlating with their negative role in the pathology of the diseases. We further show that c-MET phosphorylation is observed in established cutaneous lesions. Exposure to <jats:italic>L<\/jats:italic>. <jats:italic>mexicana<\/jats:italic> upregulated c-Met expression predominantly in infected neutrophils and c-Met expression influenced ROS release by neutrophils. In addition, pharmacological inhibition of c-MET, administrated once the lesion is established, induced a significant decrease in lesion size associated with diminished infiltration of neutrophils. Both genetic ablation of c-MET in neutrophils and systemic inhibition of c-MET locally resulted in higher levels of CD4<jats:sup>+<\/jats:sup>T cells producing IFN\u03b3, suggesting a crosstalk between neutrophils and these cells. Collectively, our data show that c-MET activation in neutrophils contributes to their recruitment following infection, and that <jats:italic>L<\/jats:italic>. <jats:italic>mexicana<\/jats:italic> induction of c-MET on neutrophils impacts the local pathology associated with this disease. Our results suggest a potential use for this inhibitor in the control of the cutaneous lesion during this parasitic infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010247","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T20:07:17Z","timestamp":1642536437000},"page":"e1010247","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["The c-MET receptor tyrosine kinase contributes to neutrophil-driven pathology in cutaneous leishmaniasis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-1323","authenticated-orcid":true,"given":"Katiuska","family":"Passelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-1370","authenticated-orcid":true,"given":"Borja","family":"Prat-Luri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5644-5047","authenticated-orcid":true,"given":"Margot","family":"Merlot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3969-7162","authenticated-orcid":true,"given":"Michiel","family":"Goris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Mazzone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3561-0207","authenticated-orcid":true,"given":"Fabienne","family":"Tacchini-Cottier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"issue":"42","key":"ppat.1010247.ref001","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1038\/onc.2016.36","article-title":"Preclinical 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