title: HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs, Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status.
abstract: HIV-1 infection is characterized by persistent viral replication, chronic immune activation, and CD4(+) T cell depletion. Moreover, several immune dysfunctions are observed in cells that are not targeted by the virus, such as B cells. Some B cell abnormalities include hypergammaglobulinemia, nonspecific B cell activation, class switching, increased cell turnover, breakage of tolerance, and a loss of the capacity to generate and maintain memory. Several cytokines and growth factors that are increased in the serum of HIV-1-infected individuals have been suggested to directly or indirectly trigger B cell activation, and one of these is BAFF. In this study, we investigate the ability of fully competent (R5-tropic) HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). We demonstrate here that HIV-1 drives BAFF production in MDMs in a type-I IFN- and TLR-independent manner. Moreover, we determine that HIV-1 Nef accessory protein is dispensable in BAFF upregulation as a nef-deleted HIV-1 strain is still able to increase BAFF at levels similar to the wild type strain. Finally, we show that the macrophage phenotype status affects HIV-1 replication and BAFF induction, as both were abrogated in MDMs displaying a M1 phenotype. This study provides new useful information about the increased levels of BAFF observed during HIV-1 infection and highlights the importance of macrophages as a source of BAFF, a phenomenon that might contribute to B cell dysfunctions at inflammatory tissue sites in infected individuals.
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and.
authors.forename: Alejandro M
authors.identifier: 0000-0001-6955-5977
authors.initials: AM
authors.lastname: Gomez
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and.
authors.forename: Michel
authors.identifier: 0000-0002-2353-7535
authors.initials: M
authors.lastname: Ouellet
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and.
authors.forename: Alexandre
authors.identifier: 0000-0003-4157-4687
authors.initials: A
authors.lastname: Deshiere
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and.
authors.forename: Yann
authors.identifier: 0000-0002-7579-7304
authors.initials: Y
authors.lastname: Breton
authors.affiliation: Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Quebec City, Quebec G1V 0A6, Canada michel.j.tremblay@crchudequebec.ulaval.ca.
authors.forename: Michel J
authors.identifier: 0000-0002-6919-7847
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D053264:B-Cell Activating Factor / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D016207:Cytokines; D007370:Interferon Type I; D034741:RNA, Small Interfering; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1