Cutting edge: myeloid differentiation factor 88 is essential for pulmonary host defense against Pseudomonas aeruginosa but not Staphylococcus aureus.
Myeloid differentiation factor 88 (MyD88) is an adapter molecule required for signal transduction via Toll-like receptors (TLRs) and receptors of the IL-1 family. Consequently, MyD88-deficient mice are highly susceptible to bacterial infections, including systemic infection with Staphylococcus aureus. To determine the role of MyD88 in innate immunity to bacterial pneumonia, we exposed MyD88-deficient and wild-type mice to aerosolized Pseudomonas aeruginosa or S. aureus. As predicted, MyD88-deficient mice failed to mount an early cytokine or inflammatory response or to control bacterial replication after infection with P. aeruginosa, which resulted in necrotizing pneumonia and death. By contrast, MyD88-deficient mice controlled S. aureus infection despite blunted local cytokine and inflammatory responses. Thus, whereas MyD88-dependent signaling is integral to the initiation of cytokine and inflammatory responses to both pathogens following infection of the lower respiratory tract, MyD88 is essential for innate immunity to P. aeruginosa but not S. aureus.
Department of Medicine, University of Washington, School of Medicine, Seattle, WA 98195, USA. shawn@u.washington.edu
Shawn J
SJ
Skerrett
H Denny
HD
Liggitt
Adeline M
AM
Hajjar
Christopher B
CB
Wilson
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009336:Necrosis; D020556:Neutrophil Infiltration / Q000235:genetics; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D018836:Inflammation Mediators; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic