Advisor(s)
Randall Q Cron
Committee Member(s)
Paul A Goepfert
Olaf Kutsch
Phillip D Smith
Lesley E Smythies
Chad Steele
Document Type
Dissertation
Date of Award
2016
Abstract
Polarization of macrophages is critical for an effective host immune response against invading pathogens. However, the HIV-1 virus can alter the cytokine/chemokine profile of polarized macrophages which may ultimately lead to their increased susceptibility to viral infection. M1 monocyte-derived macrophages (MDM) have been shown to suppress CCR5-tropic HIV-1 replication, while M2 MDM promote it. We generated M1 (GM-CSF + IFN-γ + LPS) and M2 (M-CSF + IL-4) MDM with predicted phenotypes and exposed them to a CCR5 (R5) “highly macrophage-tropic” viral strain, HIV-1BaL. M2 MDM had notably higher levels of HIV-1 infection than M1 MDM. We also investigated R5 HIV-1 transmitted founder (T/F) virus infection in polarized MDM, which had not been previously explored. Similarly, M2 MDM had higher levels of T/F infection than M1 MDM but lower compared to HIV-1BaL. Previous in vitro studies by our lab and others have shown that CD4 regulatory T cells (Tregs) suppress HIV-1 infection of primary human CD4 T cells and of neighboring non-Treg CD4 T cells. The effect of Tregs on HIV-1 infection of polarized M1 and M2 macrophages, however, remains largely unknown. We report here that Treg cells co-cultured with polarized MDM significantly increased HIV-1 infection in polarized M1 and M2 MDM. Interestingly, the results also showed that Treg co-cultures decreased HIV-1 infection in M1 MDM, but increased infection in M2 MDM (compared to conventional effector CD4 T cells) in a mechanism that was cell contact dependent. These findings suggest a role for Tregs in HIV-1 infection and tissue resident macrophages of M1 and M2 phenotype, which may contribute to the establishment and pathogenesis of HIV-1 disease.
ProQuest Publication Number
ISBN
978-1-369-45213-6
Recommended Citation
Robinson, Tanya, "CD4 Regulatory T Cells Augment HIV-1 Expression of Polarized M1 and M2 Monocyte Derived Macrophages" (2016). All ETDs from UAB. 2847.
https://digitalcommons.library.uab.edu/etd-collection/2847
Comments
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