Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a Th1 profile

GARRO, AP; CHIAPELLO, LS; BARONETTI, JL; MASIH, DT

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 vol. 132 p. 174 - 187

0019-2805

Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrate that rat peritoneal eosinophils phagocytose opsonized-live yeasts of C. neoformans, and that phenomenon involves the engagement of FcgRII and CD18. Moreover, our results show that opsonized C. neoformans phagocytosis triggers eosinophil activation, as indicated by (i) the up-regulation of MHC I, MHC II and co-stimulatory molecules; and (ii) the increase in IL-12, TNFa and IFNg production. However, NO and H2O2 synthesis by eosinophils is down-regulated after interaction with the fungus. Furthermore, this work demonstrates that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans-pulsed eosinophils proliferate in a MHC II and MHC I dependent manner, and produce important amounts of Th 1 type cytokines such as TNFa and IFNg, in the absence of Th2 cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal-antigen presenting cells and suggests that C. neoformans-loaded eosinophils might participate in the adaptive immune response.