{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:41:45Z","timestamp":1780105305152,"version":"3.54.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"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":["476926\/2011-4"],"award-info":[{"award-number":["476926\/2011-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Leishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful <jats:italic>Leishmania<\/jats:italic> infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain <jats:italic>Leishmania<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to investigate how PMNs and infected DCs interact in an <jats:italic>in vitro<\/jats:italic> model of <jats:italic>Leishmania amazonensis<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Briefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with <jats:italic>L. amazonensis<\/jats:italic>-infected DCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that <jats:italic>L. amazonensis<\/jats:italic>-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in <jats:italic>Leishmania<\/jats:italic> killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNF\u03b1 and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNF\u03b1 production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during <jats:italic>L.\u00a0amazonensis<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that the engagement of direct contact between PMNs and <jats:italic>L. amazonensis<\/jats:italic>-infected DC <jats:italic>via<\/jats:italic> DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.750648","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T07:13:50Z","timestamp":1635750830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination"],"prefix":"10.3389","volume":"12","author":[{"given":"Rafael","family":"Tiburcio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9on Dimitri","family":"Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lu\u00edsa Augusto","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Carvalho","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Suarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria M.","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Tavares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Ida","family":"Brodskyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis Worldwide and Global Estimates of Its Incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2004.03.004","article-title":"Leishmaniasis: Current Situation and New Perspectives","volume":"27","author":"Desjeux","year":"2004","journal-title":"Comp Immunology Microbiol Infect Dis"},{"key":"B3","volume-title":"World Health Organ Tech Rep Ser","year":"2010"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.actatropica.2007.08.003","article-title":"Mucosal Leishmaniasis. 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