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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
TNFR2+ regulatory T cells protect against bacteremic pneumococcal pneumonia by suppressing IL-17A-producing γδ T cells in the lung
Cell Reports, Volume 42, No. 2, Article 112054, Year 2023
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Description
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. © 2023 The Authors
Authors & Co-Authors
Xu, Rong
United Kingdom, Liverpool
University of Liverpool
Jacques, Laura C.
United Kingdom, Liverpool
University of Liverpool
Khandaker, Shadia
United Kingdom, Liverpool
University of Liverpool
French, N.
United Kingdom, Liverpool
University of Liverpool
Neill, Daniel Robert
United Kingdom, Liverpool
University of Liverpool
Kadioglu, Aras
United Kingdom, Liverpool
University of Liverpool
Statistics
Citations: 2
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1016/j.celrep.2023.112054
ISSN:
22111247