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Updated: Apr 14, 2026
Morphological and Compositional Analysis of Neutrophil Extracellular Traps Induced by Microbial and Chemical Stimuli
Published on: November 4, 2022
Eimeria bovis-triggered neutrophil extracellular trap formation is CD11b-, ERK 1/2-, p38 MAP kinase- and
Tamara Muñoz-Caro1, Sandra Jaqueline Mena Huertas2,3, Ivan Conejeros4
1Institute of Parasitology, Justus Liebig University Giessen, Schubertstraße 81, 35392, Giessen, Germany. Tamara.Munoz-Caro@vetmed.uni-giessen.de.
Abstract:
Eimeria bovis is an important coccidian parasite that causes high economic losses in the cattle industry. We recently showed that polymorphonuclear neutrophils (PMN) react upon E. bovis sporozoite exposure by neutrophil extracellular trap (NET) formation. We focused here on the molecular mechanisms that are involved in this process. The sporozoite encounter led to an enhanced surface expression of neutrophil CD11b suggesting a potential role of this receptor in E. bovis-mediated NETosis. Antibody-mediated blockage of CD11b confirmed this assumption and led to a significantly decreased sporozoite-triggered NET. In addition, E. bovis-induced NETosis was found to be Ca(2+)-dependent since the inhibition of store-operated calcium entry (SOCE) significantly diminished NET. Furthermore, NADPH oxidase, neutrophil elastase (NE) and myeloperoxidase (MPO) were confirmed as key molecules in sporozoite-triggered NETosis, as inhibition thereof blocked parasite-triggered NET. PMN degranulation analyses revealed a significant release of matrix metalloprotease-9 containing granules upon sporozoite exposure. We further show a significantly enhanced phosphorylation of ERK1/2 and p38 MAPK in sporozoite-exposed PMN indicating a key role of this signaling pathway in E. bovis-mediated NETosis. Accordingly, ERK 1/2 and p38 MAPK inhibition led to a significant decrease in NET formation. Finally, we demonstrate that sporozoite-induced NETosis is neither a stage-, species-, nor host-specific process.
Insights
Eimeria bovis sporozoites trigger neutrophil extracellular trap (NET) formation in cattle. Key molecular mechanisms involve CD11b, calcium signaling, NADPH oxidase, neutrophil elastase, and MAPK pathways, crucial for parasite-induced NETosis.
Area of Science:
- Veterinary Parasitology
- Immunology
- Molecular Biology
Background:
- Eimeria bovis causes significant economic losses in cattle.
- Neutrophil extracellular traps (NETs) are implicated in the host response to E. bovis sporozoites.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying E. bovis-induced NETosis.
- To identify key host molecules and signaling pathways involved in this innate immune response.
Main Methods:
- Antibody-mediated blockade of CD11b.
- Inhibition of store-operated calcium entry (SOCE).
- Pharmacological inhibition of NADPH oxidase, neutrophil elastase (NE), myeloperoxidase (MPO), ERK1/2, and p38 MAPK.
- Analysis of PMN degranulation and matrix metalloprotease-9 release.
Main Results:
- E. bovis sporozoite exposure enhances CD11b expression and triggers NETosis, which is dependent on CD11b and calcium influx.
- NADPH oxidase, NE, MPO, ERK1/2, and p38 MAPK are essential for parasite-induced NET formation.
- PMN degranulation releases matrix metalloprotease-9.
- The NETosis response is not specific to E. bovis life stage, species, or host.
Conclusions:
- CD11b, calcium signaling, specific enzymes (NADPH oxidase, NE, MPO), and MAPK pathways (ERK1/2, p38) are critical for E. bovis-mediated NETosis.
- These findings reveal key molecular players in the innate immune response against Eimeria bovis.
- The broad applicability suggests potential therapeutic targets for coccidiosis control.
