title: Interleukin 1 receptor-associated kinase m impairs host defense during pneumococcal pneumonia.
abstract: BACKGROUND
  Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia. Pneumococci that try to invade the lower airways are recognized by innate immune cells through pattern recognition receptors, including Toll-like receptors 2, 4, and 9. Interleukin 1 (IL-1) receptor-associated kinase (IRAK)-M is a proximal inhibitor of Toll-like receptor signaling.
  
  
  METHODS
  To determine the role of IRAK-M in host defense during pneumococcal pneumonia, IRAK-M- deficient and wild-type mice were intranasally infected with S. pneumoniae.
  
  
  RESULTS
  IRAK-M-deficient mice demonstrated a reduced lethality after infection with S. pneumoniae via the airways. Whereas bacterial burdens were similar in IRAK-M-deficient and wild-type mice early (3 hours) after infection, from 24 hours onward the number of pneumococci recovered from lungs and distant body sites were 10-100-fold lower in the former mouse strain. The diminished bacterial growth and dissemination in IRAK-M-deficient mice were preceded by an increased early influx of neutrophils into lung tissue and elevated pulmonary levels of IL-1β and CXCL1. IRAK-M deficiency did not influence bacterial growth after intravenous administration of S. pneumoniae.
  
  
  CONCLUSIONS
  These data suggest that IRAK-M impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting the early immune response.
authors.affiliation: Center for Infection and Immunity Amsterdam, University of Amsterdam, The Netherlands.
authors.forename: Gerritje J W
authors.initials: GJ
authors.lastname: van der Windt
authors.forename: Dana C
authors.initials: DC
authors.lastname: Blok
authors.forename: Jacobien J
authors.initials: JJ
authors.lastname: Hoogerwerf
authors.forename: Adriana J J
authors.initials: AJ
authors.lastname: Lammers
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Cornelis
authors.initials: C
authors.lastname: Van't Veer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000172:deficiency / Q000378:metabolism*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse