Parasite worm antigens instruct macrophages to release immunoregulatory extracellular vesicles

Area of Science:

• Immunology
• Parasitology
• Cell Biology

Background:

• Immune cells communicate via cytokines, chemokines, receptors, and extracellular vesicles (EVs).
• Parasitic worms modulate host immunity, but their impact on EV-mediated communication is unknown.
• Trichuris suis products (TSPs) are known to have immunomodulatory effects.

Purpose of the Study:

• To investigate if Trichuris suis products (TSPs) alter EV-driven communication between host immune cells.
• To determine the immunomodulatory properties of EVs released from TSPs-stimulated macrophages.
• To elucidate the mechanisms underlying the effects of these EVs.

Main Methods:

• Bone marrow-derived macrophages (BMDMs) were stimulated with TSPs.
• EVs were isolated from stimulated and unstimulated BMDMs.
• The effect of EVs on LPS-stimulated BMDMs and BMDCs was assessed by measuring cytokine release (TNFα, IL-6).
• Macrophage polarization, reactive oxygen species (ROS) production, transcriptomic, and proteomic analyses were performed.
• Pharmacological inhibition of cytochrome P450 (CYP450) was used to investigate ROS production.

Main Results:

• TSPs-pulsed BMDMs released EVs with anti-inflammatory properties, suppressing TNFα and IL-6 release in recipient immune cells.
• EVs did not induce M1 or M2 polarization in exposed macrophages.
• EVs enhanced ROS production in BMDMs, linked to deregulated redox homeostasis.
• Proteomic analysis identified CYP450 as a potential ROS source within the EVs.
• Inhibition of CYP450 reduced ROS production.

Conclusions:

• Trichuris suis products can indirectly modulate host immune responses by inducing BMDMs to release anti-inflammatory EVs.
• These EVs exert anti-inflammatory effects on recipient immune cells.
• EV-associated CYP450 contributes to ROS production and altered immune cell function.