RESUMEN

Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1ß, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.

Asunto(s)

Aspergilosis , Aspergillus fumigatus , Proteínas Fúngicas , Evasión Inmune , Proteoma , Esporas Fúngicas , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/genética , Animales , Esporas Fúngicas/inmunología , Ratones , Proteoma/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/inmunología , Aspergilosis/inmunología , Aspergilosis/microbiología , Humanos , Interacciones Huésped-Patógeno/inmunología , Interacciones Huésped-Patógeno/genética , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/metabolismo , Citocinas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/inmunología , Modelos Animales de Enfermedad , Células Epiteliales/microbiología , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino