GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology
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Updated: Aug 24, 2025
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Srinivasu Mudalagiriyappa1, Jaishree Sharma1, Miranda D Vieson2
1Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
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.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) expressing T17 cells support vaccine immunity against fungal pneumonia. These cells bolster pulmonary immunity without causing pathology, highlighting a beneficial role in infection defense.
Area of Science:
- Immunology
- Vaccinology
- Microbial Pathogenesis
Background:
- T helper 17 (Th17) cells expressing GM-CSF are implicated in autoimmune pathology.
- The role of GM-CSF+ T17 cells in anti-infective immunity, particularly vaccine responses, remains largely unknown.
- Understanding these cells is crucial for developing effective vaccines against challenging infections like fungal pneumonia.
Purpose of the Study:
- To investigate the function of GM-CSF+ T17 cells in vaccine-induced immunity against lethal fungal pneumonia.
- To elucidate the cytokine requirements for the induction and maintenance of GM-CSF+ T17 cell populations.
- To determine the role of GM-CSF+ T17 cells in protective immunity and immune memory during fungal infection.
Main Methods:
- Utilized a murine model of fungal pneumonia vaccination.
- Employed cytokine neutralization and genetic approaches to assess the roles of IL-1, IL-23, and GM-CSF.
- Analyzed T cell populations, cytokine production, and immune memory responses in the lungs post-vaccination and infection.
Main Results:
- Vaccine-induced GM-CSF+ T17 cells are essential for effective immunity against fungal pneumonia without exacerbating pathology.
- Interleukin-1 (IL-1) and IL-23, but not GM-CSF, are required for the initial induction of GM-CSF+ T17 cells post-vaccination.
- While IL-23 is dispensable for the maintenance of memory T17 and GM-CSF+ T17 cells, it is crucial for their recall response in the lungs.
Conclusions:
- GM-CSF+ T17 cells play a beneficial, non-pathological role in anti-fungal vaccine immunity.
- The induction of GM-CSF+ T17 cells is dependent on IL-1 and IL-23 signaling.
- IL-23 is critical for the effector function of memory T17 cells during recall responses to fungal infection.
