Exploring Autologous Dendritic Cells for T Cell Modulation: A Step Towards Personalized Medicine in Leishmaniasis

Area of Science:

• Immunology
• Parasitology
• Cell Biology

Background:

• Leishmaniasis, a zoonotic disease caused by Leishmania infantum, is a global health concern.
• Dendritic cells (DCs) are crucial antigen-presenting cells that link innate and adaptive immunity.
• Modulating T lymphocyte activation is key to controlling leishmaniasis.

Purpose of the Study:

• To investigate if autologous monocyte-derived dendritic cells (moDCs) primed with Leishmania infantum-derived extracellular vesicles (EVs) can direct T lymphocyte activation.
• To analyze the impact of EV priming on moDC signaling, activation, and antigen-presentation capabilities.
• To explore the resulting T cell subpopulations in co-cultures.

Main Methods:

• Co-culture of lymphocytes with Leishmania infantum-primed moDCs.
• Gene expression analysis of toll-like receptors (TLRs) and cytokines in moDCs.
• Immunophenotyping to analyze T cell subpopulations and major histocompatibility complex (MHC) molecule expression.

Main Results:

• EV-primed moDCs exhibited upregulated TLR2, TLR4, and TLR9 expression.
• Overexpression of MHC molecules was observed in EV-primed moDCs.
• Co-cultures promoted pro-inflammatory and regulatory cytokines, expanding regulatory and central memory CD8+ T cells.

Conclusions:

• Leishmania infantum-derived EVs can activate moDCs to modulate cytotoxic lymphocytes.
• This approach fosters a balanced inflammatory and regulatory immune response.
• Cell-based strategies using EV-loaded moDCs offer a potential foundation for personalized leishmaniasis therapies.