Home LiteratureArticle Details
PMID: 18835196 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses.

Immunity ·Vol. 29 ·No. 4 ·2008-10-17 ·Pages 637-49

Hall JA, Bouladoux N, Sun CM, Wohlfert EA, Blank RB, Zhu Q, Grigg ME, Berzofsky JA, Belkaid Y

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.

MeSH Terms
Adjuvants, Immunologic Animals Anti-Bacterial Agents/pharmacology CD4-Positive T-Lymphocytes/drug effects,immunology,metabolism CD8-Positive T-Lymphocytes/drug effects,immunology,metabolism DNA, Bacterial/immunology,metabolism Dendritic Cells/immunology,metabolism Immunity, Mucosal Interferon-gamma/biosynthesis,immunology Interleukin-17/biosynthesis,immunology Intestinal Mucosa/immunology Intestines/microbiology Male Mice Mice, Inbred C57BL Mice, Knockout Mucous Membrane/immunology,metabolism Signal Transduction T-Lymphocytes/immunology T-Lymphocytes, Regulatory/immunology,metabolism Toll-Like Receptor 9/immunology,metabolism
Chemicals
Adjuvants, Immunologic Anti-Bacterial Agents DNA, Bacterial Interleukin-17 Tlr9 protein, mouse Toll-Like Receptor 9 Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Hall Jason A
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Bouladoux Nicolas
Sun Cheng Ming
Wohlfert Elizabeth A
Blank Rebecca B
Zhu Qing
Grigg Michael E
Berzofsky Jay A
Belkaid Yasmine
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.08.009
Published
2008-10-17
Epub
2008-00-02
Pages
637-49
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2712925
Subset
IM
Grants
Intramural NIH HHS · Z01 AI000955-03 · United States
Corrections
CommentIn
PMID: 18957263
External Links
PubMed source DOI: 10.1016/j.immuni.2008.08.009 PMC Full Text View journal details
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