Environmental enteric dysfunction induces regulatory T cells that inhibit local CD4+ T cell responses and impair oral vaccine efficacy
Autor: | Brydie R. Huckestein, Oliver J. Harrison, Deyi Yang, Ansen H.P. Burr, Justin T. Tometich, Jason A. Hall, Sean P. Spencer, Elizabeth B. Norton, Jonathan L. Linehan, Yasmine Belkaid, Amrita Bhattacharjee, Denise Morais da Fonseca, Abigail E. Overacre-Delgoffe, Timothy W. Hand |
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Rok vydání: | 2020 |
Předmět: |
Male
Gastrointestinal Diseases Immunology Bacterial Toxins Administration Oral Mice Transgenic Biology medicine.disease_cause T-Lymphocytes Regulatory Article Cell Line Mice RAR-related orphan receptor gamma Intestine Small medicine Escherichia coli Immunology and Allergy Animals Toxin Escherichia coli Vaccines Vaccination FOXP3 Forkhead Transcription Factors Nuclear Receptor Subfamily 1 Group F Member 3 Vaccine efficacy Small intestine Mice Inbred C57BL Chronic infection Disease Models Animal Infectious Diseases medicine.anatomical_structure Drosophila Female Lymph Vaccine failure |
Zdroj: | Immunity |
ISSN: | 1097-4180 |
Popis: | Summary 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. |
Databáze: | OpenAIRE |
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