title: Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages.
abstract: Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin α(M) (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Guang Sheng
authors.initials: GS
authors.lastname: Ling
authors.affiliation: Centre for Cell Signalling and Inflammation, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Renal and Vascular Inflammation Section, Division of Immunology and Inflammation, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Woollard
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Szajna
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Liliane
authors.initials: L
authors.lastname: Fossati-Jimack
authors.affiliation: Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Scott
authors.affiliation: Centre for Cell Signalling and Inflammation, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Guido
authors.initials: G
authors.lastname: Franzoso
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007113:Immunity, Innate / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4