MyD88-dependent induction of allergic Th2 responses to intranasal antigen.
MyD88 is a common Toll-like receptor (TLR) adaptor molecule found to be essential for induction of adaptive Th1 immunity. Conversely, innate control of adaptive Th2 immunity has been shown to occur in a MyD88-independent manner. In this study, we show that MyD88 is an essential innate component in the induction of TLR4-dependent Th2 responses to intranasal antigen; thus we demonstrate what we believe to be a novel role for MyD88 in pulmonary Th2 immunity. Induction of the MyD88-independent type I IFN response to LPS is defective in the pulmonary environment. Moreover, in the absence of MyD88, LPS-induced upregulation of costimulatory molecule expression on pulmonary DCs is defective, in contrast to what has been observed with bone marrow-derived DCs (BMDCs). Reconstitution of Th2 responses occurs upon adoptive pulmonary transfer of activated BMDCs to MyD88-deficient recipients. Furthermore, the dependence of Th2 responses on MyD88 is governed by the initial route of antigen exposure; this demonstrates what we believe are novel site-specific innate mechanisms for control of adaptive Th2 immunity.
Piggott
Damani A
DA
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA. piggotda@biomed.med.yale.edu
Eisenbarth
Stephanie C
SC
Xu
Lan
L
Constant
Stephanie L
SL
Huleatt
James W
JW
Herrick
Christina A
CA
Bottomly
Kim
K
D048868:Adaptor Proteins, Signal Transducing; D000281:Administration, Intranasal; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016219:Immunotherapy, Adoptive; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C482199:lipopolysaccharide, E coli O55-B5; D010047:Ovalbumin