CD4 regulatory T cells augment HIV-1 expression of polarized M1 and M2 monocyte derived macrophages

- M2 MDM were more permissive to infection by R5 HIV-1T/F viruses than M1 MDM.
- CD4 T cells significantly increased HIV-1 expression of M1 and M2 MDM.
- Tregs differentially modulate HIV-1 infection in polarized MDM.
- Treg-mediated effects on HIV-1 expression of polarized MDM require cell contact.

Previous in vitro studies have shown that the HIV-1 virus can alter the cytokine/chemokine profile of polarized macrophages which may lead to their increased susceptibility to viral infection. Here, we found that M2 monocyte derived macrophages (MDM) were significantly more permissive to productive infection by R5-tropic HIV-1 strains, including transmitted founder (T/F) viruses, than M1 MDM. Previous in vitro studies by our lab showed that regulatory T cells (Tregs) suppress HIV-1 infection in non-Treg CD4 T cells. Here, we investigated potential inhibitory effects of Tregs on HIV-1 infection of polarized MDM. We found that Tregs significantly increased HIV-1 infection in M1 and M2 MDM via a mechanism that was cell contact dependent. These findings suggest a potential role for Tregs in HIV-1 infection of tissue resident macrophages of M1 and M2 phenotype, which may contribute to the establishment and pathogenesis of HIV-1 disease.