Molecular analyses on Neospora caninum-triggered NETosis in the caprine system.

Area of Science:

• Immunology
• Parasitology
• Veterinary Medicine

Background:

• Neospora caninum is a protozoan parasite causing significant reproductive issues in ruminants.
• Polymorphonuclear neutrophils (PMN) combat pathogens by releasing neutrophil extracellular traps (NETs).

Purpose of the Study:

• To investigate the in vitro interaction between caprine PMN and N. caninum tachyzoites.
• To characterize the NETosis process induced by N. caninum in goats and identify involved molecular pathways.

Main Methods:

• Scanning electron microscopy and immunofluorescence analysis of caprine PMN and N. caninum tachyzoites.
• Co-localization studies to identify components within NETs.
• Functional inhibition assays to determine signaling pathways involved in NETosis.

Main Results:

• Caprine PMN undergo NETosis upon contact with N. caninum tachyzoites, forming NETs that entrap the parasites.
• N. caninum-induced NETs contain DNA, histones, neutrophil elastase, pentraxin, and cathepsin B.
• NETosis is influenced by myeloperoxidase (MPO) but independent of NADPH oxidase, SOCE, ERK1/2, and p38 MAPK; PI3K-mediated autophagy inhibition does not affect NETosis.

Conclusions:

• N. caninum tachyzoites effectively induce NETosis in caprine PMN.
• This NETosis pathway differs in its molecular signaling compared to other apicomplexan parasites or host species.
• Caprine NETosis represents a crucial early host immune response during acute neosporosis.