Alejandro M. Gomez, Michel Ouellet, Alexandre Deshiere, Yann Breton and Michel J. Tremblay; HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs, Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status. Journal of Immunology (2016) May; volume 196, issue 9, pages 3806-17. doi: 10.4049/jimmunol.1501249.
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, the authors investigate the ability of fully competent (R5-tropic) HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). They demonstrate that HIV-1 drives BAFF production in MDMs in a type-I IFN- and TLR-independent manner. Moreover, they 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, the authors show that the macrophage phenotype status affects HIV-1 replication and BAFF induction, as both were abrogated in MDMs displaying an 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.
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Research funded by CIHR