Innate-adaptive immune crosstalk: TLR2 expression and CD8⁺ memory T cell responses in leprosy

Leprosy presents a clinical-immunological spectrum determined by the host immune response to Mycobacterium leprae. While paucibacillary (PB) patients mount a T_H1-polarized response with effective bacillary control, multibacillary (MB) exhibit T_Reg/T_H2 dominance and bacterial persistence. This study investigated TLR2/NF-κB-related immunophenotypic profiles in monocytes and their association with memory CD8⁺ T cell functional responses across the leprosy spectrum. Peripheral blood mononuclear cells from PB, MB, and healthy controls were stimulated with M. leprae antigen and analyzed by flow cytometry. PB patients exhibited higher frequencies of CD14⁺HLA-DR⁺TLR2⁺NF-κB⁺ monocytes and IL-12⁺ and IL-1β⁺ monocyte subsets compared to MB patients. This robust cytokine response was associated with a CD8⁺ T cell profile characterized by enhanced interferon-gamma (IFN-γ) production and reduced interleukin-10 (IL-10) expression, accompanied by increased nitric oxide (NO) production. In contrast, MB patients displayed a cytokine profile indicative of a CD8⁺ T cell response, characterized by regulatory cytokine production (diminished IFN-γ and increased IL-10), along with reduced NO production. These findings identify associations between TLR2/NF-κB-related monocyte phenotypes and distinct memory CD8⁺ T cell functional profiles across the leprosy spectrum. The higher IFN-γ/IL-10 ratio observed in PB further supports distinct effector and regulatory immune profiles between the clinical forms.