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We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how<jats:italic>Histoplasma capsulatum<\/jats:italic>load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus\u2019 EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from<jats:italic>H<\/jats:italic>.<jats:italic>capsulatum<\/jats:italic>opsonized with 6B7 was reduced, but urease activity was not altered. The uptake of<jats:italic>H<\/jats:italic>.<jats:italic>capsulatum<\/jats:italic>by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized<jats:italic>H<\/jats:italic>.<jats:italic>capsulatum<\/jats:italic>and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies<jats:italic>H<\/jats:italic>.<jats:italic>capsulatum<\/jats:italic>EV load and secretion leading to distinct effects on the host\u2019s immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.<\/jats:p>","DOI":"10.1038\/s41598-018-25665-5","type":"journal-article","created":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T11:45:51Z","timestamp":1526557551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages"],"prefix":"10.1038","volume":"8","author":[{"given":"Ludmila Matos","family":"Baltazar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zamith-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan C.","family":"Burnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-3088","authenticated-orcid":false,"given":"Hyungwon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Nimrichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4056-2695","authenticated-orcid":false,"given":"Ernesto S.","family":"Nakayasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Nosanchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,23]]},"reference":[{"key":"25665_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1006\/fgbi.2001.1311","volume":"35","author":"JP Woods","year":"2002","unstructured":"Woods, J. 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