RESIDENT ENTERIC BACTERIA ARE NECESSARY FOR DEVELOPMENT OF SPONTANEOUS COLITIS AND IMMUNE-SYSTEM ACTIVATION IN INTERLEUKIN-10-DEFICIENT MICE

Mice with targeted deletion of the gene for interleukin-10 (IL-10) spo ntaneously develop enterocolitis when maintained in conventional condi tions but develop only colitis when kept in specific-pathogen-free (SP F) environments. This study tested the hypothesis that enteric bacteri a are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were m aintained in either SPF conditions or germfree conditions or were popu lated with bacteria known to cause colitis in other rodent models. IL- 10-deficient mice kept in SPF conditions developed colitis in all segm ents of the colon (cecum and proximal and distal colon). These mice ex hibited immune system activation as evidenced by increased expression of CD44 on CD4(+) T cells; increased mesenteric lymph node cell number s; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strai ns, including Bacteroides vulgatus, known to induce colitis in other r odent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis Or immune system activation. We conclude therefor e that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mi ce.