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Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa


Kirchner, Florian R; LeibundGut-Landmann, Salomé (2021). Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa. Mucosal Immunology, 14(2):455-467.

Abstract

Keeping a stable equilibrium between the host and commensal microbes to which we are constantly exposed, poses a major challenge for the immune system. The host mechanisms that regulate homeostasis of the microbiota to prevent infection and inflammatory disorders are not fully understood. Here, we provide evidence that CD4$^{+}$ tissue-resident memory T (T$_{RM}$) cells act as central players in this process. Using a murine model of C. albicans commensalism we show that IL-17 producing CD69$^{+}$CD103$^{+}$CD4$^{+}$ memory T cells persist in the colonized tissue long-term and independently of circulatory supplies. Consistent with the requirement of Th17 cells for limiting fungal growth, IL-17-producing T$_{RM}$ cells in the mucosa were sufficient to maintain prolonged colonization, while circulatory T cells were dispensable. Although T$_{RM}$ cells were first proposed to protect from pathogens causing recurrent acute infections, our results support a central function of T$_{RM}$ cells in the maintenance of commensalism.

Abstract

Keeping a stable equilibrium between the host and commensal microbes to which we are constantly exposed, poses a major challenge for the immune system. The host mechanisms that regulate homeostasis of the microbiota to prevent infection and inflammatory disorders are not fully understood. Here, we provide evidence that CD4$^{+}$ tissue-resident memory T (T$_{RM}$) cells act as central players in this process. Using a murine model of C. albicans commensalism we show that IL-17 producing CD69$^{+}$CD103$^{+}$CD4$^{+}$ memory T cells persist in the colonized tissue long-term and independently of circulatory supplies. Consistent with the requirement of Th17 cells for limiting fungal growth, IL-17-producing T$_{RM}$ cells in the mucosa were sufficient to maintain prolonged colonization, while circulatory T cells were dispensable. Although T$_{RM}$ cells were first proposed to protect from pathogens causing recurrent acute infections, our results support a central function of T$_{RM}$ cells in the maintenance of commensalism.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Virology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Uncontrolled Keywords:Immunology, Immunology and Allergy
Language:English
Date:1 March 2021
Deposited On:16 Aug 2021 15:46
Last Modified:25 Feb 2024 02:41
Publisher:Nature Publishing Group
ISSN:1933-0219
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41385-020-0327-1
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)