Chitin Recognition via Chitotriosidase Promotes Pathologic Type-2 Helper T Cell Responses to Cryptococcal Infection
Fig 2
IL-2 Complexes Augment Type-2 Helper T Cells and Enhance Fungal Disease.
(A) CD25 expression by naïve (CD4+, CD44−), Th2- (CD4+, CD44+, IL-5-, IL-13−), and Th2+ (CD4+, CD44+, IL-5+, IL-13+) cells. (B) Cda+ Th cell numbers in the lungs of gpr4Δgpr5Δ infected mice treated with 5 μg IL-2, 25 μg anti-IL-2 antibody (JES6-1A12), or both (IL-2 Complex). Th1, Th17, and Th2 cells were identified by production of IFNγ, IL-17A, and IL-5/13, respectively. (C) Cytokines from lung homogenates of mice infected with gpr4Δgpr5Δ or age-matched naïve animals, with or without IL-2 complex treatment. (D) Pulmonary leukocytes from mice infected with gpr4Δgpr5Δ, with or without IL-2 complex treatment. (E) Cda2+ Th2 cells from lungs of mice infected with fully virulent KN99α, attenuated gpr4Δgpr5Δ, or mice infected with gpr4Δgpr5Δ and treated with IL-2 complex. (F) Survival of naïve mice or mice infected with gpr4Δgpr5Δ either with or without IL-2 complex treatment. P-value represents log-rank test comparing each survival curve with 10 mice per group to: gpr4Δgpr5Δ vs. gpr4Δgpr5Δ + IL-2 complex, P<0.0005; gpr4Δgpr5Δ vs. KN99α, P<0.0005; gpr4Δgpr5Δ + IL-2 complex vs. KN99α, P = 0.23. (G) Fungal burden within lungs of mice with or without IL-2 complex 14 days post-infection with gpr4Δgpr5Δ. (H) Hematoxylin and eosin staining of lungs from mice infected with gpr4Δgpr5Δ or similarly infected and treated with IL-2 complexes. A = brochial airway, E = epithelial cell layer. Data are presented as the mean +/- standard error with at least 2 independent experiments per group. * = P < 0.05, ** = P < 0.005, *** = P < 0.0005 by Mann-Whitney U. Cda = chitin deacetylase, CCL = chemokine ligand, DC = Dendritic Cells, IFN = interferon, IL = interleukin, ILC = Innate Lymphoid Cells, MΦ = Macrophages, NK = Natural Killer. TNF = tumor necrosis factor.