(531) Oral Pathogenic Bacterial Products Differently Modulate Responses in HIV+ and HIV– Peripheral Blood Immune Cells

Introduction/Rationale: Porphyromonas gingivalis plays key roles in the human oral microbiome and disease. Oral dysbiosis and bacterial products such as lipopolysaccharide from P. gingivalis (Pg-LPS) and lipoteichoic acid from Staphylococcus aureus (Sa-LTA) can activate peripheral immune cells, which may cross the blood brain barrier and trigger inflammation and neuronal dysfunction, leading to cognitive decline. These processes occur in people with HIV (PWH), nearly half of whom develop HIV-associated neurocognitive disorders despite antiretroviral treatment. Since oral dysbiosis affects PWH, this study characterizes the responses of HIV positive (HIV+) and HIV negative (HIV–) peripheral blood mononuclear cells (PBMCs) to Pg-LPS and Sa-LTA stimulation in vitro.

Methods: PBMCs from HIV+ and HIV– donors were cultured and exposed to Pg-LPS or Sa-LTA (0.1 or 1 µg/mL) for 24 or 48 hours (h). iNOS expression was assessed by western blot. IL-6 was quantified by ELISA, while TNF-α and IL-10 were measured via Ella multiplex system.

Results: Pg-LPS increased TNF-α in HIV– PBMCs at 48h (p=0.033); in HIV+ PBMCs, TNF-α increased at 24h (p=0.026) but declined by 48h (p=0.011). HIV+ PBMCs, 24h stimulation with Pg-LPS induced a slight increase in IL-6 secretion, which decreased by 48h (p=0.025). IL-10 levels in HIV– PBMCs remained unchanged, while in HIV+ PBMCs IL-10 was higher at 24h compared to 48h (p=0.006). No significant changes in iNOS were detected. Sa-LTA did not induce notable effects.

Conclusion: HIV+ PBMCs exhibit a pro-inflammatory response to Pg-LPS at 24h, which is not sustained for 48h. This activation appears to be counterbalanced by an anti-inflammatory response at 24h exposure. These findings suggest that oral pathogen toxins trigger distinct immune activation dynamics in PWH, potentially contributing to neuroinflammatory mechanisms. Ongoing studies include shorter stimulation times and PBMC–brain organoid co-cultures to further explore their contribution to neuronal dysfunction and cognitive impairment.