Environmental enteric dysfunction induces regulatory T cells that inhibit local CD4+ T cell responses and impair oral vaccine efficacy.

Autor:	Bhattacharjee A; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA., Burr AHP; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA; Program in Microbiology and Immunology, Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA., Overacre-Delgoffe AE; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA., Tometich JT; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA., Yang D; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA; Central South University, Xiangya School of Medicine, Changsha, PRC., Huckestein BR; Program in Microbiology and Immunology, Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA., Linehan JL; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Spencer SP; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Hall JA; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Harrison OJ; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Morais da Fonseca D; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Norton EB; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA., Belkaid Y; Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA., Hand TW; R.K. Mellon Institute for Pediatric Research, Pediatrics Department, Infectious Disease Section, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15224 USA; Program in Microbiology and Immunology, Department of Immunology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: timothy.hand@chp.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2021 Aug 10; Vol. 54 (8), pp. 1745-1757.e7. Date of Electronic Publication: 2021 Aug 03.
DOI:	10.1016/j.immuni.2021.07.005
Abstrakt:	Environmental enteric dysfunction (EED) is a gastrointestinal inflammatory disease caused by malnutrition and chronic infection. EED is associated with stunting in children and reduced efficacy of oral vaccines. To study the mechanisms of oral vaccine failure during EED, we developed a microbiota- and diet-dependent mouse EED model. Analysis of E. coli-labile toxin vaccine-specific CD4 + T cells in these mice revealed impaired CD4 + T cell responses in the small intestine and but not the lymph nodes. EED mice exhibited increased frequencies of small intestine-resident RORγT + FOXP3 + regulatory T (Treg) cells. Targeted deletion of RORγT from Treg cells restored small intestinal vaccine-specific CD4 T cell responses and vaccine-mediated protection upon challenge. However, ablation of RORγT + FOXP3 + Treg cells made mice more susceptible to EED-induced stunting. Our findings provide insight into the poor efficacy of oral vaccines in EED and highlight how RORγT + FOXP3 + Treg cells can regulate intestinal immunity while leaving systemic responses intact. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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