Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia

Fungal infections have skyrocketed in immune-compromised patients lacking cd4+ t cells,underscoring the need for vaccine prevention. an understanding of the elements that promote vaccine immunity in this setting is essential. we previously demonstrated that vaccine-induced il-17a+ cd8+ t cells (tc17) are required for resistance against lethal fungal pneumonia in cd4+ t cell-deficient hosts,whereas the individual type i cytokines ifn-γ,tnf-α and gm-csf,are dispensable. here,we report that t cell-intrinsic myd88 signals are crucial for these tc17 cell responses and vaccine immunity against lethal fungal pneumonia in mice. in contrast,ifn-γ+ cd8+ cell (tc1) responses are largely normal in the absence of intrinsic myd88 signaling in cd8+ t cells. the poor accumulation of myd88-deficient tc17 cells was not linked to an early onset of contraction,nor to accelerated cell death or diminished expression of anti-apoptotic molecules bcl-2 or bcl-xl. instead,intrinsic myd88 was required to sustain the proliferation of tc17 cells through the activation of mtor via akt1. moreover,intrinsic il-1r and tlr2,but not il-18r,were required for myd88 dependent tc17 responses. our data identify unappreciated targets for augmenting adaptive immunity against fungi. our findings have implications for designing fungal vaccines and immune-based therapies in immune-compromised patients. © 2015 nanjappa et al.