Cytokines and the regulation of fungus-specific CD4 T cell differentiation

CD4 T cells play important and non-redundant roles in protection against infection with diverse fungi. Distinct CD4 T cell subsets can mediate protection against fungal disease where Th1 and Th17 CD4 T cell subsets have been found to promote fungal clearance and protective immunity against diverse fungal pathogens. The differentiation of naïve CD4 T cells into Th1 or Th17 cells is crucially controlled by their interaction with dendritic cells and instructed by cytokines. IL-12 and IFN-γ promote Th1 differentiation while TGF-β, IL-6, IL-1, IL-21 and IL-23 promote Th17 differentiation and maintenance. The production of these cytokines by DCs is in turn regulated by innate receptors triggered in response to fungal infection. In this review we will discuss the contributions of cytokines found to influence fungus-specific CD4 T cell differentiation and their role in defense against fungal disease. We will also highlight the contributions of innate receptors involved in recognition of fungi and how they shape cytokine secretion and CD4 T cell differentiation.

► Cytokines are crucial in instructing fungus-specific CD4 T cell differentiation. ► CD4 T cells of Th1 and Th17 lineages are crucial for defense against fungal infection. ► Innate receptors shape CD4 T cell differentiation by modulation of cytokine secretion. ► Th1 versus Th17 differentiation is critically controlled by IFN-γ and IL-12. ► IL-12, IFN-γ, type IFNs, IL-23, IL-17A and IL-22 promote antifungal immunity.