title: Dual protective mechanisms of matrix metalloproteinases 2 and 9 in immune defense against Streptococcus pneumoniae.
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.
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Hong
authors.forename: Kendra J
authors.initials: KJ
authors.lastname: Greenlee
authors.forename: Ramanan
authors.initials: R
authors.lastname: Pitchumani
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
authors.forename: Li-zhen
authors.initials: LZ
authors.lastname: Song
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Pyong Woo
authors.initials: PW
authors.lastname: Park
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Akhil
authors.initials: A
authors.lastname: Bidani
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000818:Animals; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000502:physiology
chemical_list: D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D020381:Interleukin-17; D017382:Reactive Oxygen Species; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9