02580nas a2200349   4500000000100000008004100001260002500042653002400067653000900091653002600100653001400126653002000140653002200160653002400182653001400206653001900220100002400239700002200263700001400285700001800299700001300317700001500330700002000345700001300365700001400378700001500392700002000407245009800427490000800525520168300533022001402216       2026                            d  c09/2026bElsevier BV10aToll-Like Receptors10aTLR210aMycobacterium leprae 10aMonocytes10aInnate immunity10aAdaptive Immunity10aMemory CD8+ T cells10aCytokines10aFlow Cytometry1 aRodrigues-Menezes Y1 aChebli-de-Abreu N1 aMacedo JM1 aCarvalho AMRS1 aLima HBD1 aMinozzo JC1 aThomaz-Soccol V1 aCosta HS1 aDuarte MC1 aRocha MODC1 aMenezes-Souza D00aInnate-adaptive immune crosstalk: TLR2 expression and CD8+ memory T cell responses in leprosy0 v4053 a<p>Leprosy presents a clinical-immunological spectrum determined by the host immune response to <em>Mycobacterium leprae</em>. While paucibacillary (PB) patients mount a T<sub>H</sub>1-polarized response with effective bacillary control, multibacillary (MB) exhibit T<sub>Reg</sub>/T<sub>H</sub>2 dominance and bacterial persistence. This study investigated TLR2/NF-κB-related immunophenotypic profiles in monocytes and their association with memory CD8<sup>+</sup> T cell functional responses across the leprosy spectrum. Peripheral blood mononuclear cells from PB, MB, and healthy controls were stimulated with <em>M. leprae</em> antigen and analyzed by flow cytometry. PB patients exhibited higher frequencies of CD14<sup>+</sup>HLA-DR<sup>+</sup>TLR2<sup>+</sup>NF-κB<sup>+</sup> monocytes and IL-12<sup>+</sup> and IL-1β<sup>+</sup> monocyte subsets compared to MB patients. This robust cytokine response was associated with a CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.</p>
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