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

Jeong Soo Hong, Kendra J. Greenlee, Ramanan Pitchumani, Seung Hyo Lee, Li Zhen Song, Ming Shan, Seon Hee Chang, Pyong Woo Park, Chen Dong, Zena Werb, Akhil Bidani, David Corry, Farrah Kheradmand

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6427-6436
Number of pages10
JournalJournal of Immunology
Volume186
Issue number11
DOIs
StatePublished - Jun 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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