{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:20:35Z","timestamp":1790709635922,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["431857\/2018-0"],"award-info":[{"award-number":["431857\/2018-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Visceral leishmaniasis (VL) is often associated with hematologic manifestations that may interfere with neutrophil response. Lipophosphoglycan (LPG) is a major molecule on the surface of <jats:italic>Leishmania<\/jats:italic> promastigotes, which has been associated with several aspects of the parasite\u2013vector\u2013host interplay. Here, we investigated how LPG from <jats:italic>Leishmania<\/jats:italic> (<jats:italic>L<\/jats:italic>.) <jats:italic>infantum<\/jats:italic>, the principal etiological agent of VL in the New World, influences the initial establishment of infection during interaction with human neutrophils in an experimental setting <jats:italic>in vitro<\/jats:italic>. Human neutrophils obtained from peripheral blood samples were infected with either the wild-type <jats:italic>L. infantum<\/jats:italic> (WT) strain or LPG-deficient mutant (<jats:italic>\u2206lpg1<\/jats:italic>). In this setting, <jats:italic>\u2206lpg1<\/jats:italic> parasites displayed reduced viability compared to WT <jats:italic>L. infantum<\/jats:italic>; such finding was reverted in the complemented <jats:italic>\u2206lpg1<\/jats:italic>+<jats:italic>LPG1<\/jats:italic> parasites at 3- and 6-h post-infection. Confocal microscopy experiments indicated that this decreased survival was related to enhanced lysosomal fusion. In fact, LPG-deficient <jats:italic>L. infantum<\/jats:italic> parasites more frequently died inside neutrophil acidic compartments, a phenomenon that was reverted when host cells were treated with Wortmannin. We also observed an increase in the secretion of the neutrophil collagenase matrix metalloproteinase-8 (MMP-8) by cells infected with <jats:italic>\u2206lpg1 L. infantum<\/jats:italic> compared to those that were infected with WT parasites. Furthermore, collagen I matrix degradation was found to be significantly increased in <jats:italic>\u2206lpg1<\/jats:italic> parasite-infected cells but not in WT-infected controls. Flow cytometry analysis revealed a substantial boost in production of reactive oxygen species (ROS) during infection with either WT or <jats:italic>\u2206lpg1 L. infantum<\/jats:italic>. In addition, killing of <jats:italic>\u2206lpg1<\/jats:italic> parasites was shown to be more dependent on the ROS production than that of WT <jats:italic>L. infantum<\/jats:italic>. Notably, inhibition of the oxidative stress with Apocynin potentially fueled <jats:italic>\u2206lpg1 L. infantum<\/jats:italic> fitness as it increased the intracellular parasite viability. Thus, our observations demonstrate that LPG may be a critical molecule fostering parasite survival in human neutrophils through a mechanism that involves cellular activation and generation of free radicals.<\/jats:p>","DOI":"10.3389\/fcimb.2022.788196","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T04:52:28Z","timestamp":1649220748000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Leishmania infantum Defective in Lipophosphoglycan Biosynthesis Interferes With Activation of Human Neutrophils"],"prefix":"10.3389","volume":"12","author":[{"given":"Graziele","family":"Quintela-Carvalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid Madeleine Calero","family":"Goicochea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Man\u00e7ur-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayonara de Melo","family":"Viana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin da Silva","family":"Luz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Rocha Sim\u00f5es","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"L\u00e1zaro-Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Suarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Indiani","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira M.","family":"Saraiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia I.","family":"Brodskyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia T.","family":"Veras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana P.B.","family":"de Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno B.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonilson Berlink","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Descoteaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria M.","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0166-6851(03)00160-9","article-title":"Leishmania Lipophosphoglycan (LPG) Activates NK Cells Through Toll-Like Receptor-2","volume":"130","author":"Becker","year":"2003","journal-title":"Mol. 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