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

J Immunol. 2011 Jun 1;186(11):6427-36. doi: 10.4049/jimmunol.1003449. Epub 2011 Apr 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL5 / immunology
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism
  • Host-Pathogen Interactions / immunology
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Kaplan-Meier Estimate
  • Matrix Metalloproteinase 2 / deficiency
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / immunology*
  • Matrix Metalloproteinase 9 / deficiency
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phagocytosis / immunology
  • Pneumococcal Infections / genetics
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / microbiology
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pneumonia / microbiology
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / physiology

Substances

  • Chemokine CCL5
  • Chemokine CXCL10
  • Interleukin-17
  • Reactive Oxygen Species
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9