title: Regulatory T Cell Induction and Retention in the Lungs Drives Suppression of Detrimental Type 2 Th Cells During Pulmonary Cryptococcal Infection.
abstract: Lethal disease caused by the fungus Cryptococcus neoformans is a consequence of the combined failure to control pulmonary fungal replication and immunopathology caused by induced type 2 Th2 cell responses in animal models. In order to gain insights into immune regulatory networks, we examined the role of regulatory T (Treg) cells in suppression of Th2 cells using a mouse model of experimental cryptococcosis. Upon pulmonary infection with Cryptococcus, Treg cells accumulated in the lung parenchyma independently of priming in the draining lymph node. Using peptide-MHC class II molecules to identify Cryptococcus-specific Treg cells combined with genetic fate-mapping, we noted that a majority of the Treg cells found in the lungs were induced during the infection. Additionally, we found that Treg cells used the transcription factor, IFN regulatory factor 4, to dampen harmful Th2 cell responses, as well as mediate chemokine retention of Treg cells in the lungs. Taken together, induction and IFN regulatory factor 4-dependent localization of Treg cells in the lungs allow Treg cells to suppress the deleterious effects of Th2 cells during cryptococcal infection.
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Darin L
authors.initials: DL
authors.lastname: Wiesner
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Smith
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Dmitri I
authors.identifier: http://orcid.org/0000-0001-7843-1503
authors.initials: DI
authors.lastname: Kotov
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599; and.
authors.forename: Judith N
authors.initials: JN
authors.lastname: Nielsen
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Infectious Diseases and Translational Research, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Bohjanen
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Infectious Diseases and Translational Research, University of Minnesota, Minneapolis, MN 55455 knielsen@umn.edu.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000276:immunology*; D004195:Disease Models, Animal; D050835:Interferon Regulatory Factors / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019713:Receptors, CCR5 / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D019713:Receptors, CCR5; D000099218:Interferon Regulatory Factor-4; C000592874:CCR5 protein, mouse