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J Immunol. 2016 May 1;196(9):3806-17. doi: 10.4049/jimmunol.1501249. Epub 2016 Mar 28.

HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs, Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status.

Author information

1
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec G1V 4G2, Canada; and.
2
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.

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.

PMID:
27022194
DOI:
10.4049/jimmunol.1501249
[Indexed for MEDLINE]
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