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Presentation date

8-2025

College, Institute, or Department

Anesthesiology

Faculty Mentor

Georgette D. Kanmogne​

Research Mentor

Biju Bhargavan, Georgette D. Kanmogne​

Abstract

Microglia, the resident immune cells of the central nervous system (CNS), plays a pivotal role in neuroinflammation associated with HIV infection. Toll-like receptors (TLRs) are critical innate immune sensors expressed in microglia, and their dysregulation is implicated in HIV-associated neurocognitive disorders (HAND). In this preliminary study, we examined the basal expression of TLRs and the impact of HIV-Tat on their expression using the human microglial HMC3 cell line.

First, the microglial identity of HMC3 cells was confirmed by the expression of Iba1, a microglia-specific marker. RT-PCR analysis revealed basal expression of TLR2, TLR4, andTLR6, with TLR4 showing the highest expression followed by TLR6 and TLR2 under unstimulated conditions.

Treatment with recombinant HIV-Tat protein (50 ng/mL) for 24 hours resulted in a significant downregulation of TLR4 mRNA levels, with a rebound at 48 hours. Upon treatment with HIV-Tat protein, TLR6 mRNA levels were also significantly downregulated at 24 hours, with a partial recovery observed by 48 hours. Heat-inactivated Tat (HI-Tat) served as a negative control and did not significantly affect TLR expression compared to untreated controls.

These initial findings suggest that HIV-Tat selectively alters TLR expression in microglial cells, potentially contributing to CNS immune dysregulation during HIV infection. Further investigations involving a broader range of Tat concentrations and time points are necessary to validate and expand upon these observations.

Keywords

Microglia, Cells, HIV, TAT protein, Toll like receptors

HIV-1 Tat Induces Transient TLR4/6 downregulation in Human Microglia Cells: Implications for Neuroinflammation​

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