University of Leicester
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IL-1α is required for T cell-driven weight loss after respiratory viral infection

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journal contribution
posted on 2024-06-21, 13:22 authored by Ziyin Wang, Leah F Cuthbertson, Chubicka Thomas, Hadijatou J Sallah, Lucy G Mosscrop, Haoyuan Li, Tiina Talts, Kartik Kumar, Miriam F Moffatt, John S Tregoning

Respiratory viral infections remain a major cause of hospitalization and death worldwide. Patients with respiratory infections often lose weight. While acute weight loss is speculated to be a tolerance mechanism to limit pathogen growth, severe weight loss following infection can cause quality of life deterioration. Despite the clinical relevance of respiratory infection-induced weight loss, its mechanism is not yet completely understood. We utilized a model of CD 8+ T cell-driven weight loss during respiratory syncytial virus (RSV) infection to dissect the immune regulation of post-infection weight loss. Supporting previous data, bulk RNA sequencing indicated significant enrichment of the interleukin (IL)-1 signaling pathway after RSV infection. Despite increased viral load, infection-associated weight loss was significantly reduced after IL-1α (but not IL-1β) blockade. IL-1α depletion resulted in a reversal of the gut microbiota changes observed following RSV infection. Direct nasal instillation of IL-1α also caused weight loss. Of note, we detected IL-1α in the brain after either infection or nasal delivery. This was associated with changes in genes controlling appetite after RSV infection and corresponding changes in signaling molecules such as leptin and growth/differentiation factor 15. Together, these findings indicate a lung-brain-gut signaling axis for IL-1α in regulating weight loss after RSV infection.

Funding

Molecular and Cellular Basis of Infection

Wellcome Trust

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Department of Infectious Disease, Imperial College London as part of the Molecular and Cellular Basis of Infection program

History

Author affiliation

College of Life Sciences Respiratory Sciences

Version

  • VoR (Version of Record)

Published in

Mucosal Immunology

Volume

17

Issue

2

Pagination

272 - 287

Publisher

Elsevier BV

issn

1933-0219

eissn

1935-3456

Copyright date

2024

Available date

2024-06-21

Spatial coverage

United States

Language

en

Deposited by

Dr Leah Cuthbertson

Deposit date

2024-06-14