de Heleno Chagas de Carvalho Caroline, Araujo Flores Gabriela Venicia, Sandoval Pacheco Carmen Maria, da Ribeiro da Matta Vania Lucia, de Esteves de Morais Carolina, Romiti Ricardo, Belda Júnior Walter, Dalastra Laurenti Márcia
Departamento de Dermatologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Laboratório de Patologia de Moléstias Infcciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Parasite Immunol. 2025 Sep;47(9):e70026. doi: 10.1111/pim.70026.
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.
美洲皮肤利什曼病(ATL)会影响皮肤和黏膜,其病情范围由Th1/Th2反应决定。本研究调查了炎性小体激活与巨噬细胞亚群、组织寄生情况以及皮肤和黏膜皮肤利什曼病组织学变化之间的相关性。我们通过免疫组织化学评估炎性小体激活、组织寄生情况和巨噬细胞群体,并使用来自皮肤和黏膜皮肤利什曼病的29份活检样本,将其与组织病理学改变进行关联分析。与黏膜皮肤利什曼病的皮肤和黏膜病变相比,皮肤利什曼病显示出更高的寄生虫密度和受感染的巨噬细胞(p < 0.05)。CD68和CD163巨噬细胞在皮肤利什曼病中更为丰富(p < 0.0001和p < 0.05)。炎性小体标志物IL-1β和IL-18在皮肤利什曼病中显著更高(p < 0.05)。在皮肤利什曼病中,CD68巨噬细胞与炎性小体标志物呈正相关,而在黏膜皮肤利什曼病中,CD163细胞与IL-1β和半胱天冬酶-1呈强负相关。在皮肤利什曼病中,寄生虫密度与炎性小体激活呈正相关,但在黏膜皮肤利什曼病中呈负相关。研究结果表明,炎性小体激活在美洲皮肤利什曼病中发挥着不同作用。在皮肤利什曼病中,炎性小体有助于炎症反应和寄生虫清除,而在黏膜皮肤利什曼病中,它们的相关性较小,这可能是由于免疫反应更明确且寄生虫感染最少。