Chlamydia muridarum Infection Impacts Murine Models of Intestinal Inflammation and Cancer

Chlamydia muridarum has reemerged as a prevalent infectious agent in research mouse colonies. Despite its prevalence and ability to persistently colonize the murine gastrointestinal tract, few studies have evaluated the potential impact of C. muridarum on experimental models of gastrointestinal disease. Studies were conducted to evaluate the impact of C. muridarum on the Citrobacter rodentium, Trichuris muris, and Il10-/- mouse models of intestinal inflammation, as well as on tumorigenesis in the ApcMin/+ mouse following administration of dextran sodium sulfate (DSS). Naïve C57BL/6J (B6), B6.129P2-Il10tm1Cgn/J (Il10-/-), and C57BL/6J-ApcMin/J (ApcMin/+) mice were infected with C. muridarum by cohousing with chronic C. muridarum-shedding BALB/cJ mice for 2 weeks; controls were cohoused with C. muridarum-free mice. After cohousing, B6 mice (n = 8 C. muridarum infected and free) were infected with C. rodentium (109 CFU orally) or T. muris (200 ova orally). Il10-/- mice (n = 8/group with and without Helicobacter hepaticus [108 CFU/mouse] and with and without C. muridarum) and ApcMin/+ mice (n = 8/group) that received 2% DSS for 7 days in drinking water after cohousing. Mice were euthanized 14 days post-C. rodentium infection, 18 days post-T. muris infection, 60 days post-H. hepaticus infection, or control with Il10-/- mice, and 28 days post-DSS administration to ApcMin/+ mice. The severity of the cecal and colonic lesions was evaluated and graded using a tiered, semiquantitative scoring system. C. muridarum infection attenuated colitis associated with C. rodentium (P = 0.03), had no effect on T. muris-associated pathology (P = 0.22), worsened colitis in Il10-/- mice in the absence of H. hepaticus (P = 0.007), and reduced chemically induced colonic tumorigenesis in ApcMin/+ mice (P = 0.004). Thus, C. muridarum colonization differentially impacts several models of intestinal inflammation and tumorigenesis, and the presence of this bacterium in mouse colonies should be considered as a variable in these experimental readouts.