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.

Journal

Journal ID (nlm-ta): Eur J Microbiol Immunol (Bp)

Journal ID (iso-abbrev): Eur J Microbiol Immunol (Bp)

Journal ID (publisher-id): EUJMI

Title: European Journal of Microbiology & Immunology

Publisher: Akadémiai Kiadó (Budapest )

ISSN (Print): 2062-509X

ISSN (Electronic): 2062-8633

Publication date (Electronic): 21 October 2015

Publication date Collection: December 2015

Volume: 5

Issue: 4

Pages: 256-267

Affiliations

[1 ] Department of Microbiology and Hygiene, Charité – University Medicine Berlin , Berlin, Germany

[2 ] Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology/Research Center ImmunoSciences (RCIS), Charité – University Medicine Berlin , Berlin, Germany

Author notes

^* Charité – University Medicine Berlin, CC5, Department of Microbiology and Hygiene, Campus Benjamin Franklin, FEM, Garystr. 5, D-14195 Berlin, Germany; [phone]; markus.heimesaat@ 123456charite.de

Financial Disclosure, Grant Support

This work was supported by grants from the German Research Foundation (DFG) to A.F., S.B., and U.B.G. (SFB633, TP A7); A.A.K. (SFB633, TP Z1); M.M.H. and U.H. (SFB633, TP B6); A.E.K. and U.G. (SFB633, Immuco), and from the German Federal Ministery of Education and Research (BMBF) to S.B. (TP1.1).

The funders had no role in study design, data collection and analysis, decision to publish or preparation of the article.

Competing Interests

The authors declare that no competing interests exist.

Article

DOI: 10.1556/1886.2015.00033

PMC ID: 4681353

Copyright statement: © 2015, The Author(s)

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Page count

Figures: 9, Tables: 0, Equations: 0, References: 49, Pages: 12

Categories

Subject: Original Article