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Open Access Highly Accessed Research article

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

Karen L Wozniak12, Jay K Kolls3 and Floyd L Wormley12*

Author affiliations

1 Department Biology, The University of Texas at San Antonio, San Antonio, TX 78249-0062, USA

2 The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA

3 Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA

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Citation and License

BMC Immunology 2012, 13:65  doi:10.1186/1471-2172-13-65

Published: 7 December 2012

Abstract

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.

Keywords:
Gamma-delta T cells; Cryptococcus neoformans; IL-17A; Pulmonary