Work

Bidirectional Interaction Between Chronic Kidney Disease and Porphyromonas gingivalis Infection Drives Inflammation and Immune Dysfunction

Year: 2025

Type: article

Abstract: Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system’s response to infections. Our research investigates the progression of Porphyromonas gingivalis ( P. gingivalis ) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short‐term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen‐associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis . In vivo, CKD significantly enhanced P. gingivalis survival and infection‐induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis ‐infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.

Source: Journal of Immunology Research

DOI: 10.1155/jimr/8355738