title: The Role of Gelatinases in Campylobacter Jejuni Infection of Gnotobiotic Mice.
abstract: Matrix metalloproteinases (MMP)-2 and -9 (also referred to gelatinases-A and -B, respectively) are upregulated in the inflamed gut of mice and men. We recently demonstrated that synthetic gelatinase blockage reduced large intestinal pro-inflammatory immune responses and apoptosis following murine Campylobacter (C.) jejuni infection. In order to address which gelatinase mediates C. jejuni-induced immune responses, gnotobiotic MMP-2(-/-), MMP-9(-/-), and wildtype (WT) mice were generated by broadspectrum antibiotic treatment and perorally infected with C. jejuni strain 81-176. The pathogen stably colonized the murine intestinal tract irrespective of the genotype but did not translocate to extra-intestinal compartments. At days 8 and 14 postinfection (p.i.), less pronounced colonic histopathological changes were observed in infected MMP-2(-/-) mice, less distinct epithelial apoptosis, but more epithelial proliferation in both MMP-2(-/-) and MMP-9(-/-) mice, as compared to WT controls. Reduced immune responses in gelatinase-deficient mice were characterized by lower numbers of effector as well as innate and adaptive immune cells within the colonic mucosa and lamina propria. The expression of IL-22, IL-18, IL-17A, and IL-1β mRNA was higher in the colon of MMP-2(-/-) as compared to WT mice. In conclusion, both MMP-2 and MMP-9 are differentially involved in mediating C. jejuni-induced intestinal immunopathology.
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Alutis
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Grundmann
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hagen
authors.affiliation: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
keywords: Campylobacter jejuni; IL-18; IL-22; apoptosis; gelatinases; gnotobiotic mice; in vivo infection model; matrix metalloproteinases; pro-inflammatory immune responses; translocation