Mast cells (MCs) are long-lived immune cells widely distributed at mucosal surfaces and are among the first immune cell type that can get in contact with the external environment. This study aims to unravel the mechanisms of reciprocal influence between mucosal MCs and Candida albicans as commensal/opportunistic pathogen species in humans. Stimulation of bone marrow-derived mast cells (BMMCs) with live forms of C. albicans induced the release of TNF-α, IL-6, IL-13, and IL-4. Quite interestingly, BMMCs were able to engulf C. albicans hyphae, rearranging their α-tubulin cytoskeleton and accumulating LAMP1+ vesicles at the phagocytic synapse with the fungus. Candida-infected MCs increased macrophage crawling ability and promoted their chemotaxis against the infection. On the other side, resting MCs inhibited macrophage phagocytosis of C. albicans in a contact-dependent manner. Taken together, these results indicate that MCs play a key role in the maintenance of the equilibrium between the host and the commensal fungus C. albicans, limiting pathological fungal growth and modulating the response of resident macrophages during infections.

• Klíčová slova
• candida, macrophages, mast cells, microbiota, phagocytosis,
• MeSH
• Candida albicans imunologie   MeSH
• cytokiny imunologie   MeSH
• fagocytóza * MeSH
• kandidóza imunologie   patologie   MeSH
• makrofágy imunologie   fyziologie   MeSH
• mastocyty imunologie   patologie   MeSH
• membránové glykoproteiny asociované s lyzozomy imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• Lamp1 protein, mouse MeSH Prohlížeč
• membránové glykoproteiny asociované s lyzozomy MeSH

The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the alphaMbeta2 integrin receptor CD11b/CD18 (CR3 or Mac-1) and can penetrate into cytosol of professional antigen-presenting cells, such as dendritic cells. This allows us to use CyaA for delivery of passenger antigens into the cytosolic pathway of processing and MHC class I-restricted presentation, which can promote induction of antigen-specific CD8+ cytotoxic T-lymphocyte immune responses. We show here that vaccination with a genetically detoxified CyaA336/E7 protein, carrying the full-length oncoprotein E7 of the human papilloma virus 16 inserted at position 336 of the cell-invasive AC domain of CyaA, induces an E7-specific CD8+ T-cell immune response and confers on mice protective, as well as therapeutic immunity against challenge with TC-1 tumor cells expressing the E7 oncoprotein. The therapeutic efficacy of priming with the CyaA336/E7 vaccine could further be enhanced by a heterologous booster immunization with a highly attenuated modified vaccinia virus Ankara (MVA) expressing the E7 protein fused to the lysosome-associated membrane protein (LAMP1). These results establish the potential of CyaA as a new antigen delivery tool for prime/boost immunotherapy of tumors.

• MeSH
• adenylátcyklasový toxin * MeSH
• antigeny nádorové MeSH
• antigeny virové MeSH
• buněčná imunita MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dendritické buňky imunologie   MeSH
• imunoterapie metody   MeSH
• lidský papilomavirus 16 patogenita   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomavirus E7 - proteiny MeSH
• protinádorové vakcíny imunologie   MeSH
• sekundární imunizace MeSH
• virus vakcinie * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• antigeny nádorové MeSH
• antigeny virové MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• protinádorové vakcíny MeSH