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INCREASED SEVERITY OF DSS COLITIS IN MICE FOLLOWING INFECTION WITH CAMPYLOBACTER JEJUNI
JR O’Hara1, TD Feener1, L Kalischuk L1,2, AG Buret1
1Biological Sciences and Inflammation Research Network, University of Calgary, Calgary, Alberta; 2Agriculture and Agri-Food Canada, Lethbridge, Alberta
Inflammatory Bowel Disease is a relapsing inflammation of the gastrointestinal tract that is thought to result in part from an exaggerated immune response to enteric bacteria in susceptible individuals. Campylobacter jejuni, a leading cause of human enterocolitis, was recently found to exacerbate intestinal inflammation in patients with IBD via mechanisms that remain obscure.
AIM: The aim of the present study was to examine whether a prior infection with C. jejuni increases the susceptibility to and/or severity of colitis.
METHODS: C57Bl/6 mice were infected with 1 × 108 C. jejuni by oral gavage on day 1 and day 2. Following a 30 days recovery period, colitis was induced by addition of 2% DSS to the drinking water for 12 days. Sham controls and mice treated with DSS or C. jejuni alone were also assessed. Animals were weighed daily and a disease activity index (DAI) was assigned based on percent weight change, stool consistency and presence of fecal blood. Liver and spleens were examined for bacterial translocation. In vitro studies examined transepithelial resistance (TER) in confluent monolayers of human colonic epithelial cells (T84) inoculated with C.jejuni followed by LPS (2 or 10µg/mL).
RESULTS: A drop in weight was observed 8 days after addition of DSS in mice treated with C. jejuni (–3.4% ±3.3) compared to controls (2.7% ±2.5) and mice treated with DSS alone (0.01% ± 3.1). There was a significant increase in the DAI of DSS-treated mice with a prior infection compared to the three other groups (p<0.05; controls, 0; DSS, 3.2 ± 0.6, C. jejuni, 0.2 ± 0.2; C.jejuni + DSS, 5.8 ± 0.9). Gram negative bacteria were isolated from the liver of infected, DSS-treated mice. In contrast, no bacteria were recovered from the liver of controls, or from mice treated with DSS or C. jejuni alone. Furthermore, bacteria were recovered from the spleen of 60% of DSS-treated mice with a prior infection, compared to 40% from the spleen of controls and mice treated with DSS alone. In vitro data indicate that infection of T84 cells with C. jejuni or LPS alone had no effect on TER; whereas a drop in TER was noted 30 minutes after treatment of LPS in the monolayers previously exposed to C. jejuni.
CONCLUSIONS: These data indicate that a previous infection with C. jejuni may sensitize the gut leading to an increase in the severity of intestinal inflammation in susceptible hosts.
This work is supported by CAG-CIHR-CCFC