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

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-Gomes

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number445
JournalCells
Volume13
Issue number5
DOIs
Publication statusPublished - Mar 2024

Keywords

  • cytokines
  • dog
  • innate immunity
  • L. infantum
  • Leishmania amazonensis
  • Leishmania extracellular vesicles
  • major histocompatibility complex
  • pattern recognition receptors
  • peripheral blood-derived dendritic cells (moDCs)

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