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Interleukin 1 receptor-associated kinase m impairs host defense during pneumococcal pneumonia. 2012

Gerritje J W van der Windt, and Dana C Blok, and Jacobien J Hoogerwerf, and Adriana J J Lammers, and Alex F de Vos, and Cornelis Van't Veer, and Sandrine Florquin, and Koichi S Kobayashi, and Richard A Flavell, and Tom van der Poll
Center for Infection and Immunity Amsterdam, University of Amsterdam, The Netherlands.

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.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011018 Pneumonia, Pneumococcal A febrile disease caused by STREPTOCOCCUS PNEUMONIAE. Pneumococcal Pneumonia,Pneumococcal Pneumonias,Pneumonias, Pneumococcal
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013296 Streptococcus pneumoniae A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals. Diplococcus pneumoniae,Pneumococcus
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053592 Interleukin-1 Receptor-Associated Kinases A family of intracellular signaling kinases that were identified by their ability to signal from the activated INTERLEUKIN-1 RECEPTORS. Signaling from these kinases involves their interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88 and TNF RECEPTOR-ASSOCIATED FACTOR 6. IL-1 Receptor-Associated Kinase,IRAK Kinases,IRAK-1 Kinase,IRAK-2 Kinase,IRAK-3 Kinase,IRAK-4 Kinase,Interleukin-1 Receptor-Associated Kinase,Interleukin-1 Receptor-Associated Kinase 1,Interleukin-1 Receptor-Associated Kinase 2,Interleukin-1 Receptor-Associated Kinase 3,Interleukin-1 Receptor-Associated Kinase 4,IL 1 Receptor Associated Kinase,IRAK 1 Kinase,IRAK 2 Kinase,IRAK 3 Kinase,IRAK 4 Kinase,Interleukin 1 Receptor Associated Kinase,Interleukin 1 Receptor Associated Kinase 1,Interleukin 1 Receptor Associated Kinase 2,Interleukin 1 Receptor Associated Kinase 3,Interleukin 1 Receptor Associated Kinase 4,Interleukin 1 Receptor Associated Kinases,Kinase, IL-1 Receptor-Associated,Kinase, IRAK-1,Kinase, IRAK-2,Kinase, IRAK-3,Kinase, IRAK-4,Kinase, Interleukin-1 Receptor-Associated,Kinases, IRAK,Kinases, Interleukin-1 Receptor-Associated,Receptor-Associated Kinase, IL-1,Receptor-Associated Kinase, Interleukin-1,Receptor-Associated Kinases, Interleukin-1
D054884 Host-Pathogen Interactions The interactions between a host and a pathogen, usually resulting in disease. Host Pathogen Interaction,Host-Pathogen Relations,Pathogen-Host Interaction,Pathogen-Host Interactions,Host Pathogen Interactions,Host Pathogen Relations,Host-Pathogen Interaction,Host-Pathogen Relation,Interaction, Host Pathogen,Interaction, Host-Pathogen,Interaction, Pathogen-Host,Interactions, Host Pathogen,Interactions, Host-Pathogen,Interactions, Pathogen-Host,Pathogen Host Interaction,Pathogen Host Interactions,Pathogen Interaction, Host,Pathogen Interactions, Host,Relation, Host-Pathogen,Relations, Host-Pathogen

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