T Cell and Dendritic Cell Immune Responses toCryptococcus

Abstract

This chapter reviews current knowledge regarding the role of dendritic cells (DCs) and T cells in the generation of protective immunity against Cryptococcus neoformans infections. DCs function as sentinels in the innate immune system. They are the most effective antigenpresenting cells (APCs) for inducing cell-mediated immune responses and are uniquely capable of activating naive T cells. DCs phagocytose pathogens, endocytose foreign antigens, process and present antigens to T cells, and are key mediators in the initiation of adaptive immune responses. DCs are uniquely capable of decoding fungal-associated information and translating it into different adaptive Th-type immune responses. The protective immune responses correlated with accumulation of myeloid DCs in the draining lymph nodes, while nonprotective responses were associated with accumulation of lymphoid DCs. Peripheral blood mononuclear cells from HIV-infected donors have profoundly impaired proliferative and cytokine responses to cryptococcal antigens. Immunization of mice with heat-killed C. neoformans conferred protection against challenge in wild-type mice but did not induce protection in nude mice (lacking T cells), demonstrating the importance of T cells in protection in the central nervous system (CNS). The lungs and brain are the most common sites of infection for C. neoformans and C. gattii. In pulmonary, systemic, and CNS infections, Th1-type cytokines are required for a protective cell-mediated immune response. The necessity of T cells for host defenses against cryptococcosis has prompted research into identifying immunoreactive cryptococcal antigens that could serve as vaccine candidates and as diagnostic reagents to measure T-cell responses in infected or at-risk patients.