The Role of Viral and Bacterial Infections in the Etiology of Behcet's Disease

Abstract

BACKGROUND: Behcet's disease (BD) is a complex systemic vasculitis with a poorly understood etiology that involves genetic, environmental, and immunological factors. Increasing evidence suggests that viral and bacterial infections may trigger or exacerbate BD through immune-mediated pathways. This review aims to clarify how different infectious agents may contribute to BD pathogenesis. METHODS: For this review, articles addressing microbial involvement in BD were collected from established databases such as PubMed, Scopus, and Web of Science. Priority was given to studies evaluating classical pathogens-including Herpes simplex virus and Streptococcus spp.-as well as more recent agents such as SARS-CoV-2, Borrelia burgdorferi, and Helicobacter pylori. Findings from immunological, molecular, and clinical research were integrated to highlight shared mechanisms related to host-pathogen interactions. RESULTS: The reviewed literature shows that microbial infections may influence BD through multiple interconnected mechanisms. A central concept is the possible cross-reactivity between microbial and human heat shock proteins (HSPs), which may activate Th1/Th17 cytokine pathways and enhance neutrophil activity. The review also highlights the dual functions of TRIM proteins in antiviral responses and inflammatory dysregulation, as well as the involvement of inflammasome activation and pattern recognition receptors (PRRs). These combined processes may help explain how infections initiate or intensify immune responses in BD. CONCLUSION: By synthesizing current microbial and immune evidence, this review provides an updated perspective on BD immunopathogenesis and outlines testable mechanisms for future research. Understanding these links may support the development of more targeted therapeutic strategies.