Microfilariae Trigger Eosinophil Extracellular DNA Traps in a Dectin-1-Dependent Manner.

Area of Science:

• Immunology
• Parasitology
• Cell Biology

Background:

• Eosinophils are key immune cells involved in defense against parasitic infections.
• Filarial nematodes are a major cause of parasitic diseases in humans and animals.
• The precise mechanisms of eosinophil-mediated protection against filarial parasites are not fully understood.

Purpose of the Study:

• To investigate the role of eosinophil extracellular traps (EETosis) in combating filarial nematode infections.
• To identify the receptors and mechanisms involved in microfilariae-induced EETosis.
• To determine if EETosis is a conserved defense mechanism against different filarial species.

Main Methods:

• In vitro and in vivo experiments using Litomosoides sigmodontis microfilariae and L3 larvae.
• Analysis of DNA release and microfilariae motility.
• Investigation of receptor involvement using dectin-1 and other C-type lectin receptors.
• Microscopy to identify components of extracellular traps.

Main Results:

• Eosinophil extracellular traps (EETosis) are induced by microfilariae and L3 larvae of L. sigmodontis.
• EETosis inhibits microfilariae motility in a DNA- and contact-dependent manner.
• Microfilariae-injection triggers DNA release in an eosinophil-dependent manner in vivo, leading to faster clearance.
• Dectin-1 is the essential receptor for microfilariae-induced EETosis; other receptors, prior priming, and antibodies are not required.
• Extracellular DNA traps contain mitochondrial DNA and acetylated/citrullinated histones.
• EETosis is induced by both L. sigmodontis and Dirofilaria immitis (canine heartworm) in murine and human eosinophils, indicating a conserved mechanism.

Conclusions:

• Eosinophil extracellular traps (EETosis) represent a significant innate immune mechanism against filarial nematodes.
• Dectin-1-mediated recognition of microfilariae is crucial for inducing EETosis.
• EETosis provides a conserved defense strategy effective against various filarial parasites, including those affecting humans and canines.