Commensal DNA Limits Regulatory T Cell Conversion and is a Natural Adjuvant of Intestinal Immune Responses

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2008 Oct 7

PMID 18835196

Citations 263

Authors

Jason A Hall

Nicolas Bouladoux

Cheng Ming Sun

Elizabeth A Wohlfert

Rebecca B Blank

Qing Zhu

Michael E Grigg

Jay A Berzofsky

Yasmine Belkaid

Affiliations

Soon will be listed here.

Abstract

The intestinal tract is in intimate contact with the commensal microflora. Nevertheless, how commensals communicate with cells to ensure immune homeostasis is still unclear. In this study, we found that gut flora DNA (gfDNA) plays a major role in intestinal homeostasis through Toll-like receptor 9 (TLR9) engagement. Tlr9(-/-) mice displayed increased frequencies of CD4(+)Foxp3(+) regulatory T (Treg) cells within intestinal effector sites and reduced constitutive IL-17- and IFN-gamma-producing effector T (Teff) cells. Complementing this, gfDNA limited lamina propria dendritic cell-induced Treg cell conversion in vitro. Further, Treg/Teff cell disequilibrium in Tlr9(-/-) mice led to impaired immune responses to oral infection and to oral vaccination. Impaired intestinal immune responses were recapitulated in mice treated with antibiotics and were reversible after reconstitution with gfDNA. Together, these data point to gfDNA as a natural adjuvant for priming intestinal responses via modulation of Treg/Teff cell equilibrium.

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