Tight Mucosal Compartmentation of the Murine Immune Response to Antigens of the Enteric Microbiota

Astrid Konrad, Yingzi Cong, Wayne Duck, Ronald Borlaza, Charles O. Elson

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background & Aims: The normal host immune response to antigens of the enteric microbiota is poorly defined. In this study, we isolated recombinant microbial antigens from commensal bacteria and used them to probe the normal murine immune response. Methods: A plasmid DNA expression library was generated from cecal bacteria of C3H/HeJ mice and used to express 20 recombinant intestinal bacterial proteins (rIBs). Antibody responses in serum and secretions were measured by an enzyme-linked immunosorbent assay, and CD4+ T-cell responses were measured by [3H]-thymidine incorporation. Two immunodominant commensal flagellins were also tested. Results: No baseline serum immunoglobulin (Ig)G antibody or splenic CD4+ T-cell systemic response to any rIB or to either flagellin was detected in normal C3H/HeJ mice. However, there were strong systemic responses to all 20 rIBs after parenteral immunization, which were equivalent to the responses to ovalbumin. Substantial levels of intestinal IgA were detected to half the rIBs and to both commensal flagellins. Mucosal immunization with flagellin plus ovalbumin stimulated an intestinal IgA but not a serum IgG response. Antigen-pulsed dendritic cells (DCs) stimulated production of specific IgA in the absence of T-cell help via costimulation by BAFF and/or APRIL, members of the TNF family. Conclusions: The host immune response to enteric bacteria is tightly compartmentalized to the mucosa in normal mice, with systemic B cells and CD4+ T cells remaining naive rather than tolerant. We postulate that mucosal DCs play a crucial role in this compartmentation.

Original languageEnglish (US)
Pages (from-to)2050-2059
Number of pages10
JournalGastroenterology
Volume130
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

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Flagellin
Microbiota
Histocompatibility Antigens Class II
Ribs
Immunoglobulin A
T-Lymphocytes
Inbred C3H Mouse
Ovalbumin
Dendritic Cells
Immunization
Immunoglobulin G
Serum
Bacteria
Antigens
Bacterial Proteins
Enterobacteriaceae
Gene Library
Thymidine
Antibody Formation
Mucous Membrane

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Tight Mucosal Compartmentation of the Murine Immune Response to Antigens of the Enteric Microbiota. / Konrad, Astrid; Cong, Yingzi; Duck, Wayne; Borlaza, Ronald; Elson, Charles O.

In: Gastroenterology, Vol. 130, No. 7, 07.2006, p. 2050-2059.

Research output: Contribution to journalArticle

Konrad, Astrid ; Cong, Yingzi ; Duck, Wayne ; Borlaza, Ronald ; Elson, Charles O. / Tight Mucosal Compartmentation of the Murine Immune Response to Antigens of the Enteric Microbiota. In: Gastroenterology. 2006 ; Vol. 130, No. 7. pp. 2050-2059.
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