title: Opposite regulatory effects of IFN-β and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages.
abstract: CLRs are predominantly expressed in macrophages and myeloid DCs, where they play a key role in antigen recognition, scavenging, and host defense against pathogens. To identify novel immunoregulatory cytokines and networks involved in the control of these functions, we analyzed the coordinate effects of IFN-β and IL-3 on CLR expression, antigen uptake, and phagocytosis in human MDMs and MDDCs. We report that these cytokines exert opposite regulatory effects on the expression of CLRs and endocytic/phagocytic activities of MDMs. Specifically, IFN-β markedly inhibits the expression of MR and Dectin-1 during MDM differentiation and impairs the capacity of MDM to internalize antigens and phagocytose unopsonized Candida albicans. Conversely, IL-3 up-modulates MR, Dectin-1, and DC-SIGN, thus allowing more efficient uptake/phagocytosis. Interestingly, IL-3 counteracts the IFN-β effect on antigen uptake/processing by fully restoring MR expression in IFN-β-primed MDMs. In contrast, the phagocytic activity is only partially restored as a result of the failure of IL-3 in counteracting IFN-β-induced Dectin-1 suppression. Notably, IFN-β-mediated impairment of CLR expression/function occurs in macrophages but not in MDDCs. These results identify IFN-β and IL-3 as unrecognized regulators of CLR expression and function, unraveling a novel interaction between these cytokines instrumental for the regulation of the macrophage response to pathogens.
authors.affiliation: 1.Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. lucia.conti@iss.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Cardone
authors.forename: Kyojiro N
authors.initials: KN
authors.lastname: Ikeda
authors.forename: Barbara
authors.initials: B
authors.lastname: Varano
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Millefiorini
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
authors.forename: Lucia
authors.initials: L
authors.lastname: Conti
mesh_terms: D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1
chemical_list: D000941:Antigens; D015815:Cell Adhesion Molecules; D016899:Interferon-beta; D007377:Interleukin-3; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000099181:Dectin-1; C573543:MRC1 protein, human
keywords: cell differentiation; cytokines; pathogen recognition