title: Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by γδ T cells.
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.
authors.affiliation: Department Biology, The University of Texas at San Antonio, San Antonio, TX 78249-0062, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wozniak
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Floyd L
authors.initials: FL
authors.lastname: Wormley
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis*; D042541:Intracellular Space / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018925:Chemokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta