Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gamma/delta T cells

Protective responses in mice immunized with an interferon-gamma producing strain of Cryptococcus neoformans, H99γ, are associated with IL-17A production by neutrophils. Neutrophil depletion in H99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. However, we observed an increase in IL-17A in the lungs of neutrophil-depleted H99γ infected mice, which corresponded to an increase in IL-17A⁺ γδ⁺ T cells. Moreover, we observed increased IL-17A⁺/ CD3⁺ cells and IL-17A⁺/γδ⁺ cells, but decreased IL-17A⁺/Ly6G⁺ neutrophils in the lungs of IL-17 receptor (R)A deficient mice compared to wild-type mice. Increased production of IL-17A in neutropenic mice coincided with increased IL-6 and CXCL1, but not Th17 inducing cytokines TGF-β, IL-21 and IL-23. Concurrent depletion of neutrophils and γδ⁺ T cells reduced IL-17A levels. Our results suggest that γδ⁺ T cells mediate significant IL-17A production in neutropenic mice during the protective response to C. neoformans infection.