The Role of Platelet-Monocyte Binding in Macrophage Polarization and Susceptibility to HIV Infection
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Despite 30 years of research, we still do not fully understand what drives the development of disease in human immunodeficiency virus (HIV) infected individuals. An estimated 36.9 million people are living with HIV today. Platelets (PLTs) associate directly with the majority of CD16+ monocytes within the blood during acute HIV infection. CD16+ monocytes (Mos) become infected with HIV and are believed to initiate organ-based disease early in infection more than other Mo subtypes, based on studies in animal models. Once in an organ, Mos become macrophages that can harbor latent HIV in sanctuary tissues. Depending on environmental influences on the Mos, monocyte-derived macrophages (MDMs) can be polarized into subtypes with different susceptibilities to HIV infection. The effect of PLT interactions with Mos on the polarization of the progeny MDMs and the MDM’s susceptibility to HIV infection is unknown. To examine this we isolated whole blood from healthy human donors, isolated Mos, and cultured them for 7 days with or without exposure to PLTs. These MDMs were then either phenotyped or infected with HIV. When we phenotyped these MDMs we found a decrease in the percentage of M1 MDMs concurrent with an increase in expression of the HIV co-receptor CXCR4, along with a decrease in the activation markers HLA-DR, CD80, and CD163. When we infected these MDMs with HIV, we found an increase in the rate of viral production when the MDMs were exposed to PLTs, with the lowest ratio of PLTs to Mos showing the greatest effect early during infection. We believe that PLTs are affecting the polarization of the MDMs leading to an increase in the expression of receptors necessary for HIV entry, while also decreasing the ability of MDMs to initiate an immune response.