• Gerritje J W van der Windt, Dana C Blok, Jacobien J Hoogerwerf, Adriana J J Lammers, Alex F de Vos, Cornelis Van't Veer, Sandrine Florquin, Koichi S Kobayashi, Richard A Flavell, and Tom van der Poll.
• Center for Infection and Immunity Amsterdam, University of Amsterdam, The Netherlands.
• J. Infect. Dis. 2012 Jun 15;205(12):1849-57.

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.MethodsTo 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.ResultsIRAK-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.ConclusionsThese 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.

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