Eosinophils elicit proliferation of naive and fungal-specific cells in vivo so enhancing a T helper type 1 cytokine profile in favour of a protective immune response against Cryptococcus neoformans infection.

Abstract

Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, because as in healthy humans, rats can effectively contain cryptococcal infection. Moreover, it has been shown that eosinophils are components of the immune response to C.neoformans infections. In a previous in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C.neoformans, thereby triggering their activation, as indicated by the up-regulation of MHC and co-stimulatory molecules and the increase in interleukin-12, tumour necrosis factor-α and interferon-γ production. Furthermore, this work demonstrated that C.neoformans-specific CD4(+) and CD8(+) T lymphocytes cultured with these activated C.neoformans-pulsed eosinophils proliferated, and produced important amounts of T helper type 1 (Th1) cytokines in the absence of Th2 cytokine synthesis. In the present in vivo study, we have shown that C.neoformans-pulsed eosinophils are also able to migrate into lymphoid organs to present C.neoformans antigens, thereby priming naive and re-stimulating infected rats to induce T-cell and B-cell responses against infection with the fungus. Furthermore, the antigen-specific immune response induced by C.neoformans-pulsed eosinophils, which is characterized by the development of a Th1 microenvironment with increased levels of NO synthesis and C.neoformans-specific immunoglobulin production, was demonstrated to be able to protect rats against subsequent infection with fungus. In summary, the present work demonstrates that eosinophils act as antigen-presenting cells for the fungal antigen, hence initiating and modulating a C.neoformans-specific immune response. Finally, we suggest that C.neoformans-loaded eosinophils might participate in the protective immune response against these fungi.