The increased occurrence of bloody contents in the GI tract lumen was a significant change from our observations in previous experiments (Figure 5). The severity of gross pathology, particularly the fraction of mice exhibiting bloody contents in the intestinal lumen (black sections of bars), increased in passaged strains 11168, D0835, and D2600 but not in passaged strains D2586 or NW (Figure 6A-E). In previous experiments, one of 82 C. jejuni 11168 infected C57BL/6 IL-10-/- ZD1839 mice had bloody contents in the intestinal lumen (1.2%), whereas in the second and subsequent passages in this experiment, 20 of 99 (20.2%) mice infected with passaged strains had this pathology. The

single control mouse (1 of 29) having gross pathology and a high histopathology score tested negative for C. jejuni by both culture and PCR; it was thus a case of spontaneous colitis, which sometimes occurs in IL-10-deficient mice [45–48]. None of the 19 uninfected C57BL/6 IL-10-/- mice with spontaneous colitis that we have observed in either our MK0683 breeding colony or in experiments have exhibited bloody contents in the gut lumen. For each

passaged C. jejuni strain, Kruskal Wallis ANOVA was performed to determine whether differences in the level of gross pathology in mice from the four different passages of that strain were statistically significant; results were significant for strain D2600 (P = 0.047) but not for strains 11168, D2586, or D0835 (P = 0.099, 0.859, and 0.221, respectively). Figure 5 Changes in gross and histopathology caused by C. jejuni strains during serial passage (experiment 2). C57BL/6 IL-10-/- mice develop typhlocolitis

with either “”watery”" contents (primary challenge) or “”bloody”" contents (after adaptation) following oral inoculation with C. jejuni. Myosin Panels A-D show images of gross pathology; panels E-H show images of histopathology from the same mice. Panel A shows thickened cecal and colon section with watery contents in a C. jejuni infected mouse 30 days after a primary challenge with strain 11168. Panels B and D show thickened cecal and colon section with bloody contents from a C. jejuni infected mouse 30 days after challenge with adapted strain 11168. Arrow indicates greatly enlarged ileocecocolic lymph node and arrowheads point to cecal tip with dark contents. In D cecal tip is opened to expose the frank blood (arrowheads). Panel C shows the cecum and colon of a buy 4SC-202 normal sham inoculated control mouse. Panels E-H show histopathology from the same mice (E-G images taken at 10× magnification, H image taken at 40× magnification). Panel E shows mucosa of colon from the C. jejuni infected mouse with watery colon contents of Panel A. Note hyperplasia, intense mononuclear cell infiltration (white arrows) and slight neutrophilic exudates. Black arrows indicate the presence of intact epithelium. Panel F shows mucosa of colon from C. jejuni infected mouse with bloody colon contents from Panels B and D.