Xu, R, Jacques, LC, Khandaker, S, Beentjes, D, Leon-Rios, M 
ORCID: 0000-0002-7647-5454, Wei, X, French, N ORCID: 0000-0003-4814-8293, Neill, DR ORCID: 0000-0002-7911-8153 and Kadioglu, A ORCID: 0000-0003-1137-6321
(2023)
TNFR2+ regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ T cells in the lung
Cell Reports, 42 (2).
112054-.
ISSN 2211-1247, 2211-1247
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Lung, Animals, Mice, Inbred C57BL, Mice, Bacteremia, Pneumonia, Pneumococcal, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Tumor Necrosis Factor, Type II, Interleukin-17, T-Lymphocytes, Regulatory |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 03 Feb 2023 15:28 |
| Last Modified: | 24 Jan 2026 04:04 |
| DOI: | 10.1016/j.celrep.2023.112054 |
| Open Access URL: | https://www.cell.com/action/showPdf?pii=S2211-1247... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3168162 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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