In Situ Evaluation of Macrophage Populations and Inflammasome Components in Cutaneous and Mucocutaneous Leishmaniasis

American tegumentary leishmaniasis (ATL) affects the skin and mucous membranes, with a spectrum shaped by Th1/Th2 responses. This study investigated inflammasome activation in correlation with macrophage subpopulations, tissue parasitism, and histological changes in cutaneous and mucocutaneous leishmaniasis. We assessed inflammasome activation, tissue parasitism, and macrophage populations by immunohistochemistry, correlating with histopathological alterations using 29 biopsies from cutaneous and mucocutaneous leishmaniasis. Cutaneous leishmaniasis showed higher parasite density and infected macrophages than mucocutaneous leishmaniasis skin and mucosal lesions (p < 0.05). CD68⁺ and CD163⁺ macrophages were more abundant in cutaneous leishmaniasis (p < 0.0001 and p < 0.05). Inflammasome markers IL-1β⁺ and IL-18⁺ were significantly higher in cutaneous leishmaniasis (p < 0.05). In cutaneous leishmaniasis, CD68⁺ macrophages correlated positively with inflammasome markers, whereas in mucocutaneous leishmaniasis, CD163⁺ cells showed strong negative correlations with IL-1β and caspase-1. Parasite density correlated positively with inflammasome activation in cutaneous leishmaniasis but negatively in mucocutaneous leishmaniasis. Findings suggest that inflammasome activation plays different roles in ATL. In cutaneous leishmaniasis, inflammasomes contribute to the inflammatory response and parasite clearance, while in mucocutaneous leishmaniasis, they are less relevant, possibly due to a more defined immune response with minimal parasitism.