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Immunol."],"abstract":"<jats:p>In this study, the human immune response mechanisms against<jats:italic>Sporothrix brasiliensis<\/jats:italic>and<jats:italic>Sporothrix schenckii<\/jats:italic>, two causative agents of human and animal sporotrichosis, were investigated. The interaction of<jats:italic>S. brasiliensis<\/jats:italic>and<jats:italic>S. schenckii<\/jats:italic>with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of<jats:italic>Sporothrix<\/jats:italic>yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two<jats:italic>Sporothrix<\/jats:italic>yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the<jats:italic>Sporothrix<\/jats:italic>yeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1\u03b2 secretion by hMDM in response to both<jats:italic>S. brasiliensis<\/jats:italic>and<jats:italic>S. schenckii<\/jats:italic>, suggesting that the host complement system plays an essential role in the inflammatory immune response against these<jats:italic>Sporothrix<\/jats:italic>species. Nevertheless, the structural differences in the PRMs of the two<jats:italic>Sporothrix<\/jats:italic>species, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system and<jats:italic>via<\/jats:italic>CR3 receptor mediating an inflammatory response to<jats:italic>Sporothrix<\/jats:italic>species.<\/jats:p>","DOI":"10.3389\/fimmu.2021.749074","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T06:51:10Z","timestamp":1636959070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans"],"prefix":"10.3389","volume":"12","author":[{"given":"Gabriela W. 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