MyD88 Mediates Neutrophil Recruitment Initiated by IL-1R but Not TLR2 Activation in Immunity against Staphylococcus aureus

• Published in: Immunity (Cambridge, Mass.) Vol. 24; no. 1; pp. 79 - 91
• Main Authors: Miller, Lloyd S., O'Connell, Ryan M., Gutierrez, Miguel A., Pietras, Eric M., Shahangian, Arash, Gross, Catherine E., Thirumala, Ajaykumar, Cheung, Ambrose L., Cheng, Genhong, Modlin, Robert L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2006; Elsevier Limited
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Bioluminescence; Bone Marrow Cells - metabolism; Chemokines - genetics; Chemokines - metabolism; Cytokines - genetics; Cytokines - metabolism; Defects; Experiments; Histology; Mice; Mice, Mutant Strains; Myeloid Differentiation Factor 88; Neutrophil Infiltration - genetics; Protein expression; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; Rodents; Scholarships & fellowships; Skin - immunology; Skin - pathology; Staphylococcal Skin Infections - genetics; Staphylococcal Skin Infections - immunology; Staphylococcal Skin Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus infections; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Wound healing
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2005.11.011

MyD88 is an important signaling adaptor for both TLR and IL-1R family members. Here, we evaluated the role of TLR2/MyD88 and IL-1R/MyD88 signaling in host defense against S. aureus by using a cutaneous infection model in conjunction with bioluminescent bacteria. We found that lesions of S. aureus-infected MyD88- and IL-1R-deficient mice were substantially larger with higher bacterial counts compared with wild-type mice. In contrast, TLR2-deficient mice had lesions that were only moderately larger with minimally higher bacterial counts. In addition, MyD88- and IL-1R- but not TLR2-deficient mice had severely decreased recruitment of neutrophils to the site of infection. This neutrophil recruitment was not dependent upon IL-1R/MyD88 signaling by recruited bone marrow-derived cells, suggesting that resident skin cells utilize IL-1R/MyD88 signaling to promote neutrophil recruitment.