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Publication : Dual protective mechanisms of matrix metalloproteinases 2 and 9 in immune defense against Streptococcus pneumoniae.

First Author  Hong JS Year  2011
Journal  J Immunol Volume  186
Issue  11 Pages  6427-36
PubMed ID  21508260 Mgi Jnum  J:173212
Mgi Id  MGI:5013544 Doi  10.4049/jimmunol.1003449
Citation  Hong JS, et al. (2011) Dual Protective Mechanisms of Matrix Metalloproteinases 2 and 9 in Immune Defense against Streptococcus pneumoniae. J Immunol 186(11):6427-36
abstractText  A localized and effective innate immune response to pathogenic bacterial invasion is central to host survival. Identification of the critical local innate mediators of lung defense against such pathogens is essential for a complete understanding of the mechanism(s) underlying effective host defense. In an acute model of Streptococcus pneumoniae lung infection, deficiency in matrix metalloproteinase (MMP)2 and MMP9 (Mmp2/9(-/-)) conferred a survival disadvantage relative to wild-type mice treated under the same conditions. S. pneumoniae-infected Mmp2/9(-/-) mice recruited more polymorphonuclear leukocytes to the lung but had higher bacterial burdens. Mmp2/9(-/-) mice showed significantly higher levels of IL-17A, IP-10, and RANTES in the lung. Although MMP2-dependent cleavage partially inactivated IL-17A, MMP9 was critical for effective bacterial phagocytosis and reactive oxygen species generation in polymorphonuclear neutrophils. These data demonstrate critical nonredundant and protective roles for MMP2 and MMP9 in the early host immune response against S. pneumoniae infection.
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