title: HIV-1-triggered release of type I IFN by plasmacytoid dendritic cells induces BAFF production in monocytes.
abstract: HIV-1 infection leads to numerous B cell abnormalities, including hypergammaglobulinemia, nonspecific B cell activation, nonspecific class switching, increased cell turnover, breakage of tolerance, increased immature/transitional B cells, B cell malignancies, as well as a loss of capacity to generate and maintain memory, all of which contribute to a global impairment of the immune humoral compartment. Several cytokines and soluble factors, which are increased in sera of HIV-1-infected individuals, have been suggested to directly or indirectly contribute to these B cell dysfunctions, and one of these is the B cell-activating factor (BAFF). We report in this study that HIV-1 (X4- and R5-tropic) upregulates BAFF expression and secretion by human monocytes. Moreover, we show that the virus-mediated production of BAFF by monocytes relies on a type I IFN response by a small percentage of plasmacytoid dendritic cells (pDCs) present in the monocyte cultures. HIV-1-induced type I IFN by pDCs triggers BAFF production in both classical and intermediate monocytes, but not in nonclassical monocytes, which nonetheless display a very strong basal BAFF production. We report also that basal BAFF secretion was higher in monocytes obtained from females compared with those from male donors. This study provides a novel mechanistic explanation for the increased BAFF levels observed during HIV-1 infection and highlights the importance of pDC/monocyte crosstalk to drive BAFF secretion.
authors: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec - Pavillon Centre Hospitalier de l'Université Laval, Quebec, Quebec G1V 4G2, Canada; and.
authors: Alejandro M
authors: AM
authors: Gomez
authors: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec - Pavillon Centre Hospitalier de l'Université Laval, Quebec, Quebec G1V 4G2, Canada; and.
authors: Michel
authors: M
authors: Ouellet
authors: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec - Pavillon Centre Hospitalier de l'Université Laval, Quebec, Quebec G1V 4G2, Canada; and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Quebec, Quebec G1V 0A6, Canada michel.j.tremblay@crchul.ulaval.ca.
authors: Michel J
authors: MJ
authors: Tremblay
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000378:metabolism*; D016899:Interferon-beta / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D011070:Poly I-C / Q000494:pharmacology; D061251:Primary Cell Culture; D011804:Quinolines / Q000494:pharmacology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists / Q000235:genetics / Q000276:immunology
chemical_list: C557465:1-(2-methylpropyl)-1H-imidazo(4,5-c)quinolin 4-amine; D053264:B-Cell Activating Factor; D016898:Interferon-alpha; D011804:Quinolines; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D016899:Interferon-beta; D011070:Poly I-C