Cryptococcal infection and Th1-Th2 cytokine balance

Abstract

Cytokines have been recognized as key factors in determining host resistance to infectious pathogens. In particular, Th1-Th2 cytokine balance in hosts is profoundly associated with the outcome of infection caused by intracellular microbes. In a murine model of pulmonary and disseminated infection with Cryptococcus neoformans, an opportunistic fungal pathogen that frequently leads to fatal meningoencephalitis in severely immunocompromised hosts, expression of cytokine mRNA in the lungs from infected animals revealed Th2-dominant profiles, while administration of IL-12, which rescued mice from fatal infection, converted such balance toward Th1-dominant states in a drastic fashion. Thus, commitment of Th phenotypes critically determines host sensitivity to cryptococcal infection. In this review, we described how Th1-Th2 cytokine balance influences host protective responses to C. neoformans, and we identify the host and pathogen factors that regulate such balance.