Regulatory T cell induction and retention in the lungs drives suppression of detrimental type 2 Th cells during pulmonary cryptococcal infection

Darin L. Wiesner, Kyle D. Smith, Dmitri I. Kotov, Judith N. Nielsen, Paul R. Bohjanen, Kirsten Nielsen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalJournal of Immunology
Volume196
Issue number1
DOIs
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant AI080275 (to K.N.). D.L.W. received support from National Institutes of Health T32 Training Grant AI007313, a University of Minnesota Doctoral Dissertation Fellowship, and a Dennis W. Watson Fellowship. We thank Dr. Calvin Williams (Medical College of Wisconsin) for kindly providing Foxp3-cre mice, as well as Dr. Marc Jenkins for helpful discussions. We also thank the University of Minnesota Flow Cytometry Core Facility for instrumentation and the University of North Carolina Lineberger Comprehensive Cancer Center Animal Histopathology Core Facility.

Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.

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