Avaliação da expressão dos receptores Toll-like 1/2 e de mediadores da imunidade inata e adaptativa em pacientes com hanseníase

Abstract

Introduction: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, remains a public health challenge due to its complex pathogenesis and the wide range of immune responses that determine its clinical forms. Objectives: This study aimed to investigate the role of intracellular and surface markers on leukocytes – particularly Toll-like receptors (TLRs) – in modulating the immune response and influencing clinical polarization of the disease. Methods: Peripheral blood samples were collected from newly diagnosed leprosy patients classified into paucibacillary (PB) and multibacillary (MB) forms. The expression and function of immune markers were evaluated after in vitro stimulation with soluble M. leprae antigen. Study groups included PB patients (n=17), MB patients (n=15), and healthy controls (n=31). Flow cytometry was used to assess surface markers on monocyte-derived macrophages (CD14, HLA-DR, TLR1, TLR2) and lymphocytes (CD3, CD4, CD45RO), as well as intracellular markers in macrophages (NF-κB, IL-1β, IL-12) and lymphocytes (IFN-γ, IL-10). Results: MB patients showed a significantly higher bacilloscopic index (25.2-fold increase; p < 0.0001) compared to PB patients. In CD14⁺HLA-DR⁺TLR1⁺TLR2⁺NF-κB⁺ macrophages, the PB group had higher percentages of IL-12-producing cells (1.6-fold increase compared to controls, p = 0.0046; 2.3-fold increase compared to MB, p = 0.0046) and IL-1β-producing cells (1.6-fold increase compared to controls, p = 0.0147; 1.9-fold increase compared to MB, p = 0.0192), with similar findings for IMF. In CD4⁺CD45RO⁺ T lymphocytes, the PB group showed higher IFN-γ production (2.6 times higher than MB, p = 0.0012), whereas IL-10 was higher in the MB group (2.2 times higher than PB, p = 0.0054). The IFN-γ/IL-10 ratio was substantially higher in PB patients, both in cell percentages (28.5-fold increase, p < 0.05) and IMF (5.14-fold increase, p < 0.05). Conclusion: Our findings demonstrate significant immunological differences between PB and MB forms, with a predominant TH1 response in PB and a regulatory profile in MB, underscoring the critical role of TLRs and cytokines in leprosy polarization.