title: T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis.
abstract: Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2. Infection with the yeast-like pathogen Cryptococcus neoformans is usually controlled by a Th1-mediated immune response. The mechanisms responsible for nonprotective Th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. Using a murine pulmonary model of C. neoformans infection, we report that T1/ST2 expression correlates with the intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44 and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally, T1/ST2-driven Th2 development resulted in defective pulmonary fungal control. These data demonstrate that T1/ST2 directs Th2 cell activation and polyfunctionality in allergic bronchopulmonary mycosis.
authors.affiliation: Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Piehler
authors.forename: A
authors.initials: A
authors.lastname: Grahnert
authors.forename: M
authors.initials: M
authors.lastname: Eschke
authors.forename: T
authors.initials: T
authors.lastname: Richter
authors.forename: G
authors.initials: G
authors.lastname: Köhler
authors.forename: W
authors.initials: W
authors.lastname: Stenzel
authors.forename: G
authors.initials: G
authors.lastname: Alber
mesh_terms: D000818:Animals; D001996:Bronchopneumonia / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D003453:Cryptococcosis / Q000276:immunology* / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D017472:Receptors, Interleukin-1