The myeloid differentiation factor 88 is dispensable for the development of a delayed host response to Pseudomonas aeruginosa lung infection in mice.
Because MyD88 transduces a core set of Toll-like receptor (TLR)-induced signals, microbial-induced host responses can be divided broadly into the MyD88-dependent and MyD88-independent pathways. A specific pathogen induces a distinct pattern of host response dependent upon the signalling pathways employed. Recently, we demonstrated that a MyD88-dependent pathway is essential for the development of early (4-8 h) host response to Pseudomonas aeruginosa lung infection. Here, we show that the development of a delayed (24-48 h) host response to P. aeruginosa is independent of MyD88. Using MyD88-deficient mice, the production of macrophage inflammatory protein 2, tumour necrosis factor and interleukin 1alpha in the airway was observed following P. aeruginosa lung infection for 24 or 48 h. Moreover, the MyD88-deficient mice recruited sufficient neutrophils in the lung and cleared the bacteria efficiently from the lung after 48 h. Thus, the full development of host responses to P. aeruginosa lung infection involves, in a sequential, stepwise fashion, a MyD88-dependent early response and a MyD88-independent delayed mechanism.
Power
M R
MR
Department of Microbiology and Immunology, Dalhousie University, Canada.
Marshall
J S
JS
Yamamoto
M
M
Akira
S
S
Lin
T-J
TJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002630:Chemotactic Factors / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000096:biosynthesis; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D002630:Chemotactic Factors; D016207:Cytokines; D018836:Inflammation Mediators; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D009195:Peroxidase