Expression ratio of PD-1 on the T cell surface and TGF-β levels in acute and chronic brucellosis: A marker of immune evasion

Background: Brucellosis is considered a zoonotic disease characterized by the ability of Brucella spp. to evade host immune responses and establish chronic infections. Key immune-regulatory molecules, such as transforming growth factor-beta (TGF-β) and programmed death-1 (PD-1), may play a central role in this immune evasion. Objective: The present study had a gold target to compare the expression of PD-1 on CD4⁺ and CD8⁺ T cells, as well as serum levels of TGF-β level between patients with acute or chronic brucellosis relative to those in healthy controls. It also aimed to assess their prospective roles as immunological markers of advancing and persistent disease. Methods: In the present study, we recruited a total of 60 confirmed brucellosis patients , about 30 of both acute and chronic, as well as 30 healthy controls. The enzyme-linked immunosorbent assay was reliant on the measurement of serum TGF-β levels, and flow cytometry assisted in the identification of PD-1 expression among CD4 ⁺ and CD8 ⁺ T cells. Correlation analyses were conducted to explore the relationship between TGF-β levels and PD-1 expression. Results: Patients with acute brucellosis exhibited significantly higher levels of PD-1 on CD4⁺ and CD8⁺ T lymphocytes than that of chronic patients and healthy individuals (P < 0.05). Patients with chronic brucellosis also showed increased PD-1 levels compared with controls. No significant difference was found between both acute and chronic brucellosis stages but serum level of TGF-β in both cases differed significantly from control (P < 0.05). Plasma TGF-β was highly positively correlated with PD-1 expression (r = 0.99, P < 0.0001) indicating that they could act co-operatively to suppress immunity. Novelty: The present study sheds novel light on the immunological basis of brucellosis infection, especially about immune escape. It illustrates the correlation of PD-1 expression with TGF-β levels, as a biomarker for disease monitoring and also as a therapeutic target. These results provide a new insight into the host–pathogen interplay that may contribute to designing therapeutic interventions for reactivating antimicrobial immune responses in chronic brucellosis. Conclusion: The ultimate conclusions of our study are that the immune suppression in patients infected with brucellosis infections is due to the product of higher levels serum TGF-β and increased expression levels of PD-1 on CD4⁺ and CD8⁺ T cells. The strong association of TGF-β and PD-1 suggests a controlling program that facilitates Brucella persistence. The examined markers look to be promising targets for therapy of immunological dysfunction in chronic brucellosis and could serve as the indicators for the monitoring of disease. Keywords: Brucellosis, chronic infection (CI), immune evasion, PD-1, TGF-β, T cell exhaustion.