Salmonella-superspreader hosts require gut regulatory T cells to maintain a disease-tolerant state
(2025) In The Journal of experimental medicine 222(11). p.1-17- Abstract
Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission. Treg depletion in SSP mice resulted in decreased survival, heightened gut inflammation, and impairment of the intestinal barrier, without affecting Salmonella persistence. Colonic Tregs from SSP mice exhibited a unique... (More)
Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission. Treg depletion in SSP mice resulted in decreased survival, heightened gut inflammation, and impairment of the intestinal barrier, without affecting Salmonella persistence. Colonic Tregs from SSP mice exhibited a unique transcriptomic profile characterized by the upregulation of type 1 inflammatory genes, including the transcription factor T-bet. In the absence of Tregs, we observed robust expansion of cytotoxic CD4+ T cells, with CD4+ T cell depletion restoring homeostasis. These results uncover a critical host strategy to establish disease tolerance during chronic enteric infection, providing novel insights into mucosal responses to persistent pathogens and chronic intestinal inflammation.
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- author
- Di Luccia, Blanda ; Massis, Liliana M. ; Butler, Daniel S.C. LU ; Narasimhan, Ramya ; Ruddle, Sarah J. ; Pham, Trung H.M. ; Vilches-Moure, José G. and Monack, Denise M.
- publishing date
- 2025-11-03
- type
- Contribution to journal
- publication status
- published
- in
- The Journal of experimental medicine
- volume
- 222
- issue
- 11
- article number
- e20242431
- pages
- 1 - 17
- publisher
- Rockefeller University Press
- external identifiers
-
- scopus:105015484461
- pmid:40924026
- ISSN
- 1540-9538
- DOI
- 10.1084/jem.20242431
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2025 Di Luccia et al.
- id
- 35743310-5af9-4c3c-974e-88a3ec69f2dc
- date added to LUP
- 2026-09-09 15:42:10
- date last changed
- 2026-09-10 08:16:33
@article{35743310-5af9-4c3c-974e-88a3ec69f2dc,
abstract = {{<p>Host-pathogen interactions involve two critical strategies: resistance, whereby hosts clear invading microbes, and tolerance, whereby hosts carry high pathogen burden asymptomatically. Here, we investigate mechanisms by which Salmonella-superspreader (SSP) hosts maintain an asymptomatic state during chronic infection. We found that regulatory T cells (Tregs) are essential for this disease-tolerant state, limiting intestinal immunopathology and enabling SSP hosts to thrive, while facilitating Salmonella transmission. Treg depletion in SSP mice resulted in decreased survival, heightened gut inflammation, and impairment of the intestinal barrier, without affecting Salmonella persistence. Colonic Tregs from SSP mice exhibited a unique transcriptomic profile characterized by the upregulation of type 1 inflammatory genes, including the transcription factor T-bet. In the absence of Tregs, we observed robust expansion of cytotoxic CD4+ T cells, with CD4+ T cell depletion restoring homeostasis. These results uncover a critical host strategy to establish disease tolerance during chronic enteric infection, providing novel insights into mucosal responses to persistent pathogens and chronic intestinal inflammation.</p>}},
author = {{Di Luccia, Blanda and Massis, Liliana M. and Butler, Daniel S.C. and Narasimhan, Ramya and Ruddle, Sarah J. and Pham, Trung H.M. and Vilches-Moure, José G. and Monack, Denise M.}},
issn = {{1540-9538}},
language = {{eng}},
month = {{11}},
number = {{11}},
pages = {{1--17}},
publisher = {{Rockefeller University Press}},
series = {{The Journal of experimental medicine}},
title = {{Salmonella-superspreader hosts require gut regulatory T cells to maintain a disease-tolerant state}},
url = {{http://dx.doi.org/10.1084/jem.20242431}},
doi = {{10.1084/jem.20242431}},
volume = {{222}},
year = {{2025}},
}