Exploiting Leishmania-Primed Dendritic Cells as Potential Immunomodulators of Canine Immune Response

利用利什曼原虫引发的树突状细胞作为犬免疫反应的潜在免疫调节剂

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作者:Ana Valério-Bolas, Mafalda Meunier, Joana Palma-Marques, Armanda Rodrigues, Ana Margarida Santos, Telmo Nunes, Rui Ferreira, Ana Armada, João Carlos Alves, Wilson Antunes, Inês Cardoso, Sofia Mesquita-Gabriel, Lis Lobo, Graça Alexandre-Pires, Luís Marques, Isabel Pereira da Fonseca, Gabriela Santos-

Abstract

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 Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum 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, L. amazonensis 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.

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