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- W4313356569 abstract "Abstract Macrophages are HIV-1 targets but relatively resistant to HIV-1 cytotoxicity. Effector macrophages can be functionally polarized into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes. M1 monocyte-derived macrophages (MDM) suppress CCR5 (R5) HIV-1 replication, while M2 MDM promote it. While CD4 regulatory T cells (Tregs) inhibit HIV-1 infection of primary CD4 T cells in co-culture, their effect on MDM infection is unknown. We generated M1 (GM-CSF+IFNγ+LPS) and M2 (M-CSF+IL-4) MDM with predicted phenotypes and infected them with R5 HIV-1BAL reporter viruses. M2 MDM had notably higher infection than M1 MDM. To explore acute stages of infection, we infected M1 and M2 MDM with 3 different R5 HIV-1 transmitted founder (T/F) viruses. Similarly, M2 MDM had higher levels of T/F HIV-1 infection than M1 MDM but lower compared to HIV-1BAL. To investigate the role of Tregs on HIV-1 infection of MDM, we co-cultured Tregs with HIV-1 infected MDM. Treg co-cultures yielded decreased HIV-1 infection of M1 but increased infection of M2 MDM. Surprisingly, Tregs mediate divergent effects on HIV-1 infection of M1 and M2 MDM. A transwell system was used to explore if Treg effects on HIV-1 infection of MDM were cell contact and/or cytokine dependent. Similar to co-culture, Tregs (compared to effector T cells) in the transwell system with HIV-1 infected polarized MDM led to decreased HIV-1 infection of M1 but increased infection of M2 MDM. However, the level of infection was significantly lower in the transwell system compared to co-culture, suggesting optimal Treg mediated effects require cell-contact. We are currently studying the roles of CTLA-4, IL-10, and TGFβ in Treg suppressive activity on HIV-1 infection of MDM to explore the mechanism." @default.
- W4313356569 created "2023-01-06" @default.
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- W4313356569 date "2016-05-01" @default.
- W4313356569 modified "2023-09-23" @default.
- W4313356569 title "Regulatory CD4+ T cells differentially modulate HIV-1 infection of polarized M1 and M2 macrophages" @default.
- W4313356569 doi "https://doi.org/10.4049/jimmunol.196.supp.147.14" @default.
- W4313356569 hasPublicationYear "2016" @default.
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