MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus.
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.
Miller
Lloyd S
LS
Division of Dermatology, David Geffen School of Medicine at UCLA, 52-121 CHS, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
O'Connell
Ryan M
RM
Gutierrez
Miguel A
MA
Pietras
Eric M
EM
Shahangian
Arash
A
Gross
Catherine E
CE
Thirumala
Ajaykumar
A
Cheung
Ambrose L
AL
Cheng
Genhong
G
Modlin
Robert L
RL
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D020556:Neutrophil Infiltration / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000473:pathology; D013207:Staphylococcal Skin Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2