Valério-Bolas Ana, Meunier Mafalda, Palma-Marques Joana, Rodrigues Armanda, Santos Ana Margarida, Nunes Telmo, Ferreira Rui, Armada Ana, Alves João Carlos, Antunes Wilson, Cardoso Inês, Mesquita-Gabriel Sofia, Lobo Lis, Alexandre-Pires Graça, Marques Luís, Pereira da Fonseca Isabel, Santos-Gomes Gabriela
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal.
Divisão de Medicina Veterinária, Guarda Nacional Republicana, 1200-771 Lisbon, Portugal.
Cells. 2024 Mar 3;13(5):445. doi: 10.3390/cells13050445.
Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naïve T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to and parasites and their extracellular vesicles (EVs). increased toll-like receptor 4 gene expression in synergy with nuclear factor κB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8 T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies.
树突状细胞(DCs)捕获病原体并处理抗原,在激活初始T细胞方面发挥关键作用,架起了固有免疫和获得性免疫之间的桥梁。然而,对于DCs面对寄生虫时的激活情况知之甚少。因此,本研究调查了犬外周血来源的DCs(moDCs)暴露于 和 寄生虫及其细胞外囊泡(EVs)后的体外活性。 与核因子κB激活协同作用增加了Toll样受体4基因表达以及促炎细胞因子的产生。这种寄生虫还诱导了主要组织相容性复合体(MHC)II类分子的表达,并上调了共刺激分子CD86,这与趋化因子CXCL16的释放一起,可吸引并有助于T淋巴细胞的激活。相比之下, 诱导moDCs产生促炎和抗炎细胞因子的混合物,表明这种寄生虫可与DCs建立不同的免疫关系。EVs促进moDCs表达与共刺激分子上调及CXCL16释放相关的I类MHC,表明EVs可调节moDCs以吸引细胞毒性CD8 T细胞。因此,这些寄生虫及其EVs可塑造DC激活。对DC激活的详细了解可能为先进的利什曼病控制策略的开发开辟新途径。