Intestinal colonization regulates systemic anti-commensal immune sensitivity and hyperreactivity

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Host-microbial mutualism depends on regulating immune responses to intestinal microbiota.
• Commensal bacteria regularly enter systemic circulation, causing bacteremia that the immune system must manage.
• While non-pathogenic, commensal bacteria are immunogenic and can elicit systemic immune reactions.

Purpose of the Study:

• To investigate how systemic immune sensitivity to commensal bacteria is regulated.
• To determine if early colonization with a microbiota influences systemic immune responses to commensal bacteria.

Main Methods:

• Germ-free mice and mice colonized at birth were used.
• A modified Escherichia coli strain with an added T helper cell epitope on outer membrane porin C (OmpC) was introduced systemically.
• T cell-dependent IgG responses to E. coli were measured following systemic priming.

Main Results:

• Germ-free mice showed heightened systemic immune sensitivity and hyperreactivity to the modified E. coli.
• This increased sensitivity was demonstrated by elevated E. coli-specific IgG responses.
• Mice colonized at birth did not exhibit this heightened systemic immune sensitivity.
• The increased immunogenicity was linked to the OmpC modification, not loss of function.

Conclusions:

• Early colonization with a gut microbiota regulates systemic immune sensitivity to commensal bacteria.
• The systemic immune system exhibits increased sensitivity to modified commensal bacteria in the absence of a microbiota.
• This suggests a crucial role for the gut microbiota in educating the systemic immune system.