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Infection and Immunity, October 2006, p. 5513-5521, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00730-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Inhibition of Matrix Metalloproteinases Protects Mice from Ascending Infection and Chronic Disease Manifestations Resulting from Urogenital Chlamydia muridarum Infection

Muhammad T. Imtiaz,1 Justin H. Schripsema,1 Ira M. Sigar,1 John N. Kasimos,2 and Kyle H. Ramsey1*

Departments of Microbiology and Immunology,1 Department of Pathology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 605152

Received 5 May 2006/ Returned for modification 27 June 2006/ Accepted 20 July 2006

Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix molecules. We have previously reported enhanced expression of matrix metalloproteinases in Chlamydia muridarum urogenital tract infection of female mice. Kinetics and patterns of MMP expression as well as enhanced expression in susceptible strains of mice in the prior study implied a role for MMP in pathogenesis. To explore this further, we infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril and a chemically modified tetracycline) and reserved infected sham-treated mice as controls. Neither of the treatments affected shedding of viable chlamydiae from the lower urogenital tract, but the administration of either MMPi protected mice from the formation of hydrosalpinx—a surrogate marker of oviduct occlusion and infertility. Interestingly, the mechanism of protection for mice treated with chemically modified tetracycline 3, appeared to be related to prevention of ascending upper genital tract infection. These results imply that MMP are involved in pathogenesis of chlamydial infection in this model by mediating ascension of the infection into the upper genital tract.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, 555 31st St., Downers Grove, IL 60516. Phone: (630) 515-6165. Fax: (630) 515-7245. E-mail: kramse{at}midwestern.edu.

Editor: F. C. Fang

Infection and Immunity, October 2006, p. 5513-5521, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00730-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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