title: Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis.
abstract: Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ΔdblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ΔdblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Piehler
authors.forename: Werner
authors.initials: W
authors.lastname: Stenzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Grahnert
authors.forename: Josephin
authors.initials: J
authors.lastname: Held
authors.forename: Lydia
authors.initials: L
authors.lastname: Richter
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.forename: Tina
authors.initials: T
authors.lastname: Richter
authors.forename: Maria
authors.initials: M
authors.lastname: Eschke
authors.forename: Gottfried
authors.initials: G
authors.lastname: Alber
authors.forename: Uwe
authors.initials: U
authors.lastname: Müller
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007136:Immunoglobulins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology; D008172:Lung Diseases, Fungal / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*
chemical_list: D007136:Immunoglobulins; D015847:Interleukin-4