TNFR2<SUP>+</SUP> regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing y? T cells in the lung

Xu, Rong, Jacques, Laura C, Khandaker, Shadia, Leon-Rios, Miguel, Beentjes, Daan, Wei, Xiaoqing, French, Neil ORCID: 0000-0003-4814-8293, Neill, Daniel R ORCID: 0000-0002-7911-8153 and Kadioglu, Aras ORCID: 0000-0003-1137-6321 (2023) TNFR2<SUP>+</SUP> regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing y? T cells in the lung. CELL REPORTS, 42 (2). 112054-.

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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 and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	03 Feb 2023 15:28
Last Modified:	18 Oct 2023 08:58
DOI:	10.1016/j.celrep.2023.112054
Open Access URL:	https://www.cell.com/action/showPdf?pii=S2211-1247...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3168162