Characterization of platelet signature on monocytes isolated from HIV infected individuals

Abstract

Abstract Background Higher levels of platelet-monocyte complexes (PMCs) are detected in human immunodeficiency virus (HIV)-infected individuals. Such complexes are implicated in expansion of monocytes exhibiting inflammatory phenotype, and their translocation into tissues, thus promoting development of cerebrovascular and cardiovascular disorders. Here we have recruited small sub-set of HIV-infected individuals to investigate how platelets cause epigenetic changes in monocytes of HIV-infected individuals. We posit that the formation of PMCs facilitates monocyte differentiation via exchange of biomaterial between activated platelets and monocytes during HIV-infection. Methods We performed ATAC-seq to measure changes in chromatin accessibility from two types of monocytes, PMC-derived or non-PMC-derived, isolated from HIV-infected persons. Results Using ATAC-Seq data, we were able to detect distinct changes in chromatin accessibility patterns within the genomic regions of proinflammatory mediators in PMC-derived monocytes. Chromatin accessibility of inflammatory genes was dramatically increased in PMC-derived monocytes. This suggested to us a possibility of active exchange of molecules that causes such alterations in monocytes. Conclusions Increases in chromatin accessibility of pro-inflammatory genes occur in the PMC-derived monocytes in persons with HIV. This change is likely due to the transfer of platelet antigens to monocytes via cell-cell interaction, suggesting a novel mechanism through which platelets trigger inflammatory response in monocytes. Thus, our initial findings pave a way that has a strong diagnostic as well as therapeutic value.