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Infection and Immunity, January 2005, p. 661-665, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.661-665.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Tissue Inhibitor of Metalloproteinase 1 Regulates Resistance to Infection

Marie Mei Lee,1,{dagger} Bong-June Yoon,1 Keith Osiewicz,1 Michael Preston,2 Brian Bundy,1 Anna M. van Heeckeren,3 Zena Werb,4 and Paul D. Soloway1,5*

Roswell Park Cancer Institute, Buffalo,1 Division of Nutritional Sciences, Cornell University, Ithaca, New York,5 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts,2 Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio,3 Department of Anatomy, University of California, San Francisco, California4

Received 21 July 2004/ Returned for modification 27 August 2004/ Accepted 24 September 2004

Tissue inhibitor of metalloproteinase 1 (TIMP-1)-deficient mice are resistant to Pseudomonas aeruginosa corneal infections. Corneas healed completely in TIMP-1-deficient mice, and infections were cleared faster in TIMP-1-deficient mice than in wild-type littermates. Genetic suppression studies using matrix metalloproteinase (MMP)-deficient mice showed that MMP-9, MMP-3, and MMP-7 but not MMP-2 or MMP-12 are needed for resistance. Increased resistance was also seen during pulmonary infections. These results identify a novel pathway regulating infection resistance.

* Corresponding author. Present address: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853. Phone: (607) 254-6444. Fax: (607) 254-6444. E-mail: pds28{at}cornell.edu.

Editor: F. C. Fang

{dagger} Present address: University of California, San Francisco, CA 94122.

Infection and Immunity, January 2005, p. 661-665, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.661-665.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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