Posters
HIV and Bacterial LPS Synergistically Activate AIM2 Inflammasome in Primary Human Oral Keratinocytes
Presenting Author Academic/Professional Position
Graduate Student
Academic Level (Author 1)
Graduate Student
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: HIV infection profoundly disrupts the oral microbiome, increasing the presence of Gram-negative bacteria such as Porphyromonas gingivalis (P. gingivalis), which is detected in over 80% of cases. P. gingivalis secretes lipopolysaccharide (LPS), a potent immune stimulant that can damage primary human oral keratinocytes (HOK) even in antiretroviral therapy (cART) treated people with HIV (PWH). HOK cells respond to bacterial and viral stimuli by activating inflammasome complexes, including AIM2, a DNA-sensing inflammasome protein. While LPS alone is known to trigger canonical and non-canonical pathways, leading to inflammasome activation, our study investigates how HIV exposure synergizes with LPS to induce the inflammatory response in HOK. We hypothesize that HIV exposure primes HOK cells to enhance AIM2 activation in response to LPS, contributing to increased chronic inflammation and immune dysregulation - among PWH.
Methods: HOK were treated with different P. gingivalis LPS (pgLPS) concentrations (1 ng, 10 ng, 100 ng, 1 μg) for 96 hours, and gene expression changes in NLRP3, CASPASE 1, AIM2, CASPASE 4, and CASPASE 5 were analyzed via qPCR. Additionally, HOK were exposed to HIV for 24 hours, followed by 24-hour LPS treatment, to assess the impact of HIV on LPS-induced inflammation.
Results: In cells treated with LPS alone, NLRP3, CASPASE 4, and CASPASE 5 increased by ~1.5-fold at 1 ng of LPS. At 10 ng, NLRP3 increased 1.4-fold, CASPASE 1 increased 3.5-fold, and AIM2 increased 2.5-fold. At 100 ng, NLRP3 rose 2.4-fold, CASPASE 1 increased 2.6-fold, and AIM2 reached 3.2-fold. At 1 μg, CASPASE 4 increased 2-fold and AIM2 3-fold. Pre-exposure to HIV-1 followed by 1 ng LPS led to a 10-fold increase in CASPASE 5 and an 8-fold increase in AIM2 (p=0.0013). At 10 ng, CASPASE 5 and AIM2 increased 9-fold (p<0.0001). At 100 ng, all three genes increased 2-fold. HIV alone caused a 3-fold increase in AIM2 with no other changes
Conclusion: Our study established that there is a synergistic effect of HIV and LPS in driving AIM2 inflammasome activation in HOK cells. While LPS alone upregulated AIM2 in a dose-dependent manner, HIV pre-exposure significantly increased the AIM2 activation and other associated proteins such as CASPASEs, especially at lower LPS concentrations. This heightened activation, along with increased CASPASE 5 expression, suggests HIV primes HOK for enhanced inflammasome responses, potentially contributing to persistent inflammation in oral cavity. AIM2 emerges as a key player and potential therapeutic target for reducing chronic inflammation among PWH.
Recommended Citation
Jamil, Md Shafayat; Roy, Deepa; Roy, Upal; Rodrigo, Hansapani; Sahoo, Nirakar; and Xu, Chun, "HIV and Bacterial LPS Synergistically Activate AIM2 Inflammasome in Primary Human Oral Keratinocytes" (2025). Research Symposium. 182.
https://scholarworks.utrgv.edu/somrs/2025/posters/182
Included in
Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Immunology and Infectious Disease Commons
HIV and Bacterial LPS Synergistically Activate AIM2 Inflammasome in Primary Human Oral Keratinocytes
Background: HIV infection profoundly disrupts the oral microbiome, increasing the presence of Gram-negative bacteria such as Porphyromonas gingivalis (P. gingivalis), which is detected in over 80% of cases. P. gingivalis secretes lipopolysaccharide (LPS), a potent immune stimulant that can damage primary human oral keratinocytes (HOK) even in antiretroviral therapy (cART) treated people with HIV (PWH). HOK cells respond to bacterial and viral stimuli by activating inflammasome complexes, including AIM2, a DNA-sensing inflammasome protein. While LPS alone is known to trigger canonical and non-canonical pathways, leading to inflammasome activation, our study investigates how HIV exposure synergizes with LPS to induce the inflammatory response in HOK. We hypothesize that HIV exposure primes HOK cells to enhance AIM2 activation in response to LPS, contributing to increased chronic inflammation and immune dysregulation - among PWH.
Methods: HOK were treated with different P. gingivalis LPS (pgLPS) concentrations (1 ng, 10 ng, 100 ng, 1 μg) for 96 hours, and gene expression changes in NLRP3, CASPASE 1, AIM2, CASPASE 4, and CASPASE 5 were analyzed via qPCR. Additionally, HOK were exposed to HIV for 24 hours, followed by 24-hour LPS treatment, to assess the impact of HIV on LPS-induced inflammation.
Results: In cells treated with LPS alone, NLRP3, CASPASE 4, and CASPASE 5 increased by ~1.5-fold at 1 ng of LPS. At 10 ng, NLRP3 increased 1.4-fold, CASPASE 1 increased 3.5-fold, and AIM2 increased 2.5-fold. At 100 ng, NLRP3 rose 2.4-fold, CASPASE 1 increased 2.6-fold, and AIM2 reached 3.2-fold. At 1 μg, CASPASE 4 increased 2-fold and AIM2 3-fold. Pre-exposure to HIV-1 followed by 1 ng LPS led to a 10-fold increase in CASPASE 5 and an 8-fold increase in AIM2 (p=0.0013). At 10 ng, CASPASE 5 and AIM2 increased 9-fold (p<0.0001). At 100 ng, all three genes increased 2-fold. HIV alone caused a 3-fold increase in AIM2 with no other changes
Conclusion: Our study established that there is a synergistic effect of HIV and LPS in driving AIM2 inflammasome activation in HOK cells. While LPS alone upregulated AIM2 in a dose-dependent manner, HIV pre-exposure significantly increased the AIM2 activation and other associated proteins such as CASPASEs, especially at lower LPS concentrations. This heightened activation, along with increased CASPASE 5 expression, suggests HIV primes HOK for enhanced inflammasome responses, potentially contributing to persistent inflammation in oral cavity. AIM2 emerges as a key player and potential therapeutic target for reducing chronic inflammation among PWH.
