GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology

Srinivasu Mudalagiriyappa, Jaishree Sharma, Miranda D. Vieson, Som Gowda Nanjappa

Research output: Contribution to journalArticlepeer-review

Abstract

GM-CSF co-expressing T17 cells instigate pathologic inflammation during autoimmune disorders, but their function in immunity to infections is unclear. Here, we demonstrate the role of GM-CSF+ Tc17 cells for vaccine immunity against lethal fungal pneumonia and the cytokine requirements for their induction and memory homeostasis. Vaccine-induced GM-CSF+ Tc17 cells are necessary to bolster pulmonary fungal immunity without inflating pathology. Although GM-CSF expressing Tc17 cells preferentially elevate during the memory phase, their phenotypic attributes strongly suggest they are more like Tc17 cells than IFNγ-producing Tc1 cells. IL-1 and IL-23, but not GM-CSF, are necessary to elicit GM-CSF+ Tc17 cells following vaccination. IL-23 is dispensable for memory Tc17 and GM-CSF+ Tc17 cell maintenance, but recall responses of effector or memory Tc17 cells in the lung require it. Our study reveals the beneficial, nonpathological role of GM-CSF+ Tc17 cells during fungal vaccine immunity.

Original languageEnglish (US)
Article number111543
JournalCell Reports
Volume41
Issue number4
DOIs
StatePublished - Oct 25 2022

Keywords

  • CP: Immunology
  • GM-CSF
  • GM-CSF Tc17 cells
  • IL-1
  • IL-17A
  • IL-23
  • fungal
  • immunity
  • pathology
  • vaccine

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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