| Full text | |
| Author(s): Show less - |
Fachi, Jose L.
;
de Oliveira, Sarah
;
Trsan, Tihana
;
Penati, Silvia
;
Gilfillan, Susan
;
Cao, Siyan
;
Castro, Pollyana Ribeiro
;
Fernandes, Mariane Font
;
Hyrc, Krzysztof L.
;
Liu, Xiuli
;
Rodrigues, Patrick Fernandes
;
Bhattarai, Bishan
;
Layden, Brian T.
;
Vinolo, Marco Aurelio R.
;
Colonna, Marco
Total Authors: 15
|
| Document type: | Journal article |
| Source: | CELL HOST & MICROBE; v. 33, n. 2, p. 25-pg., 2025-02-12. |
| Abstract | |
Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4+ intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2). While acetate activation of FFAR2 on epithelial cells helps resist CDI, it does not directly regulate MHC-II expression. Instead, MHC-II is regulated by FFAR2 in type 3 innate lymphoid cells (ILC3s). Acetate enhances interleukin-22 (IL-22) production by ILC3s, which then suppresses MHC-II expression on the colonic epithelium. In conclusion, a low-fiber diet reduces acetate- induced IL-22 production by ILC3s, leading to increased MHC-II on the colonic epithelium. This change affects recovery from CDI by expanding the population of pathogenic CD4+ IELs. (AU) | |
| FAPESP's process: | 21/09155-3 - Analysis of the role of the FFAR2 receptor in neutrophil functionality and myelopoiesis |
| Grantee: | Sarah de Oliveira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation |
| Grantee: | Marco Aurélio Ramirez Vinolo |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 23/00393-4 - Role of the acetate-FFAR2 axis on granulopoiesis and IL-22 production by intestinal neutrophils |
| Grantee: | Sarah de Oliveira |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 17/06577-9 - Mechanisms involved in the protective effect of short-chain fatty acids against Clostridium difficile-associated colitis |
| Grantee: | José Luís Fachi |
| Support Opportunities: | Scholarships in Brazil - Doctorate |