TNFR2+ regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ T cells in the lung

Rong Xu, Laura C Jacques, Shadia Khandaker, Daan Beentjes, Miguel Leon-Rios, Xiaoqing Wei, Neil French, Daniel R Neill, Aras Kadioglu

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
41 Downloads (Pure)

Abstract

Streptococcus pneumoniae is a pathogen of global morbidity and mortality. Pneumococcal pneumonia can lead to systemic infections associated with high rates of mortality. We find that, upon pneumococcal infection, pulmonary Treg cells are activated and have upregulated TNFR2 expression. TNFR2-deficient mice have compromised Treg cell responses and highly activated IL-17A-producing γδ T cell (γδT17) responses, resulting in significantly enhanced neutrophil infiltration, tissue damage, and rapid development of bacteremia, mirroring responses in Treg cell-depleted mice. Deletion of total Treg cells predominantly activate IFNγ-T cell responses, whereas adoptive transfer of TNFR2+ Treg cells specifically suppress the γδT17 response, suggesting a targeted control of γδT17 activation by TNFR2+ Treg cells. Blocking IL-17A at early stage of infection significantly reduces bacterial blood dissemination and improves survival in TNFR2-deficient mice. Our results demonstrate that TNFR2 is critical for Treg cell-mediated regulation of pulmonary γδT17-neutrophil axis, with impaired TNFR2+ Treg cell responses increasing susceptibility to disease.

Original languageEnglish
Article number112054
JournalCell Reports
Volume42
Issue number2
Early online date30 Jan 2023
DOIs
Publication statusPublished - 28 Feb 2023

Keywords

  • CP: Immunology
  • IL-17A
  • Streptococcus pneumoniae
  • TNFR2
  • bacteremia
  • neutrophilic inflammation
  • pneumococcal disease
  • pneumococcus
  • regulatory T cell
  • respiratory disease
  • γδ T cell

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'TNFR2+ regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ T cells in the lung'. Together they form a unique fingerprint.

Cite this