Cytokines and costimulatory molecules: positive and negative regulation of the immune response to Cryptococcus neoformans.

Cytokines are small proteins or glycoproteins that transmit information from one cell to another. Most cells in the body secrete and respond to cytokines and their effects have been described on a myriad of cellular functions. Cytokine interactions may not be linear, thus making the system extremely intricate and with unpredictable features. Therefore, each model of disease may be unique, with its own mechanism of autoregulation dictated by positive and negative feedback involving cytokines and costimulatory molecules. The emergence of some cytokines over others in the course of Cryptococcus neoformans infection may characterize a positive or negative outcome of cryptococcosis. Much less is known about the influence of costimulatory molecules in regulating C. neoformans immune response. The available information indicates a critical role for proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 12 (IL-12). The positive role of interferon gamma in infected tissue as an inducer of antimicrobial function of innate immune cells and as positive feedback for IL-12 induction appears to be indisputable. In vitro studies indicate that costimulatory molecule expression appears to be regulated on antigen-presenting cells by C. neoformans and increased expression of B7-1 and CD40 on these cells may promote a protective response. These studies await confirmation in an in vivo system. The interplay between cytokines and costimulatory molecules has been scarcely explored and additional details are needed to better understand how they convey positive and negative information to immune cells in response to C. neoformans.