title: Antibody-opsonized bacteria evoke an inflammatory dendritic cell phenotype and polyfunctional Th cells by cross-talk between TLRs and FcRs.
abstract: During secondary immune responses, Ab-opsonized bacteria are efficiently taken up via FcRs by dendritic cells. We now demonstrate that this process induces cross-talk between FcRs and TLRs, which results in synergistic release of several inflammatory cytokines, as well as altered lipid metabolite profiles. This altered inflammatory profile redirects Th1 polarization toward Th17 cell responses. Interestingly, GM-CSF-producing Th cells were synergistically evoked as well, which suggests the onset of polyfunctional Th17 cells. Synergistic cytokine release was dependent on activation via MyD88 and ITAM signaling pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via transcription-dependent mechanisms for TNF-α and IL-23 and posttranscriptional mechanisms for caspase-1-dependent release of IL-1β. Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic cells. In conclusion, our results support that bacteria alone initiate fundamentally different immune responses compared with Ab-opsonized bacteria through the combined action of two classes of receptors and, ultimately, may refine new therapies for inflammatory diseases.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, 1007 MB Amsterdam, the Netherlands; Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; J.Bakema@vumc.nl.
authors.forename: Jantine E
authors.initials: JE
authors.lastname: Bakema
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands;
authors.forename: Cornelis W
authors.initials: CW
authors.lastname: Tuk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands;
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands;
authors.forename: Sven C
authors.initials: SC
authors.lastname: Bruijns
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; Immunaffect BV, 1404 AK Bussum, the Netherlands;
authors.forename: Joost B
authors.initials: JB
authors.lastname: Vos
authors.affiliation: Department of Metabolic Diseases, Netherlands Metabolomics Centre, University Medical Centre Utrecht, Utrecht 3584 EA, the Netherlands; and.
authors.forename: Sophia
authors.initials: S
authors.lastname: Letsiou
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands;
authors.forename: Christien D
authors.initials: CD
authors.lastname: Dijkstra
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands;
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.affiliation: Department of Metabolic Diseases, Netherlands Metabolomics Centre, University Medical Centre Utrecht, Utrecht 3584 EA, the Netherlands; and.
authors.forename: Arjan B
authors.initials: AB
authors.lastname: Brenkman
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, the Netherlands; Department of Surgery, VU University Medical Center, 1081 BT Amsterdam, the Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D011961:Receptors, Fc; D051193:Toll-Like Receptors