Theses and Dissertations

Date of Award

5-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology

First Advisor

Upal Roy

Second Advisor

Nirakar Sahoo

Third Advisor

Hansapani Rodrigo

Abstract

Human immunodeficiency virus type 1 (HIV-1) remains a major global health concern, affecting approximately 39 million people worldwide, with 500,000 new infections reported in 2022. While combined antiretroviral therapy (cART) has significantly reduced viral replication, HIV-1 infection is linked to various comorbidities, including oral dysbiosis and accelerated aging. Immune dysregulation in HIV-1–infected individuals promotes the proliferation of pathogenic gram-negative bacteria like Porphyromonas gingivalis, a key contributor to periodontal disease. P. gingivalis secretes lipopolysaccharide (LPS), which adversely affects human oral keratinocytes (HOK), the first line of defense against microbial threats in the oral cavity. HOK recognize LPS as a threat, triggering inflammasome formation via canonical and non-canonical pathways. Key inflammasome components—NLRP3, AIM2, and caspases (CASP1, 4, and 5)—activate pro-inflammatory cytokines such as IL-1β, IL-18, and TNF. While these cytokines help manage microbial threats, their excessive production may lead to chronic inflammation and tissue damage, exacerbating periodontal disease. Pyroptosis, an inflammatory form of programmed cell death, further contributes to tissue destruction. This thesis explores the hypothesis that HIV-1–induced immune dysregulation primes HOK for heightened inflammasome activation upon exposure to P. gingivalis LPS, leading to sustained inflammation and periodontal deterioration. Understanding the molecular mechanisms underlying inflammasome hyperactivation and pyroptosis in HIV-1–infected oral tissues could inform therapeutic strategies. Targeting inflammasome regulation or cytokine release may help mitigate periodontal disease and systemic complications in immunocompromised patients, improving clinical management of HIV-associated oral health issues.

Comments

Copyright 2025 Md Shafayat Jamil. https://proquest.com/docview/3240621821

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