Tight mucosal compartmentation of the murine immune response to antigens of the enteric microbiota.
OBJECTIVE
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.
Konrad
Astrid
A
Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA.
Cong
Yingzi
Y
Duck
Wayne
W
Borlaza
Ronald
R
Elson
Charles O
CO
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005408:Flagellin / Q000378:metabolism; D007111:Immunity, Cellular; D018928:Immunity, Mucosal / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D010047:Ovalbumin / Q000378:metabolism; D012016:Reference Values; D012680:Sensitivity and Specificity
D015704:CD4 Antigens; D004269:DNA, Bacterial; D005408:Flagellin; D010047:Ovalbumin