Expression of Matrix Metalloproteinases Subsequent to UrogenitalChlamydia muridarumInfection of Mice

Abstract

The central hypothesis of this study was that matrix metalloproteinases (MMPs) would be enhanced following murine chlamydial infection and that their expression would vary in mouse strains that differ in their susceptibility to chronic chlamydia-induced disease. To address this hypothesis, female C3H/HeN and C57BL/6 mice were infected intravaginally with Chlamydia muridarum. Uterine and oviduct tissues were assessed for transcription of MMP genes and their tissue inhibitors. An increased activity of MMP genes relative to preinfection tissues was observed in the C3H/HeN mice when compared to C57BL/6 mice. Using gelatin zymography, we detected constitutive MMP-2 activity in both strains of mice but an increase in MMP-9. Casein zymography indicated the presence of two elastase-like activities consistent with MMP-12 and possibly MMP-7. Western blotting and antigen capture enzyme-linked immunoassay also confirmed an increase in MMP-9 but constitutive MMP-2 expression subsequent to the infection in both strains of mice. In C57BL/6 mice, MMP-9 was present in monomer and dimer form throughout the 56-day monitoring period. C3H/HeN mice produced dimeric MMP-9, but increases in the monomer form were also observed through day 14. Post-translational modification of MMP-9 between the two strains also differed. Immunohistochemistry revealed neutrophils as a prominent source for MMP-9 in both strains of mice. We conclude that differences in the relative expression and activity of MMPs, particularly MMP-9, occur in mice differing in their susceptibility to the development of chronic chlamydial disease. These differences may account for disparate outcomes with regard to chronic sequelae of the disease.

Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of GenitalChlamydia muridarumInfection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production

“…rCPAFϩIL-12-vaccinated animals also had lower frequen- (4,25,41). Therefore, reduction of PMN infiltration into the oviductal and mesosalpingeal tissues at an earlier point during the course of chlamydial infection also might account for the observed protection against upper genital tract pathology in vaccinated mice.…”

Genetic variation at the TNF locus and the risk of severe sequelae of ocular Chlamydia trachomatis infection in Gambians

“…34 TNF is highly expressed during episodes of conjunctival inflammation in these subjects with trichiasis (M Burton, personal communication) and may influence risk of disease progression in relation to the spectrum of TNF-inducible genes, such as matrix metalloprotease 9 that may be important in initiating fibrosis. 35,36 We studied SNPs capturing common genetic variation within 25 kb of genome within the MHC region. The study suggests that host genetic variation at the TNF locus may affect risk of severe trachoma, but also that variation affecting related neighboring genes such as LTA, whose role in infectious, autoimmune and other disorders has started to be defined 13,[37][38][39] may be important.…”

Interleukin-17 Contributes to Generation of Th1 Immunity and Neutrophil Recruitment duringChlamydia muridarumGenital Tract Infection but Is Not Required for Macrophage Influx or Normal Resolution of Infection

“…However, elevated levels of IL-17 have been associated with increased disease susceptibility during C. muridarum respiratory tract infection via recruitment of neutrophils (16,47). Enhanced neutrophil influx and neutrophil release of matrix metalloproteases has been directly linked to tissue pathology in mouse models of C. muridarum genital tract infection (34,37). In addition, human studies have suggested that increased neutrophil activation has been associated with increased genital tract disease in females infected with C. trachomatis (43).…”