Eimeria bovis-triggered neutrophil extracellular trap formation is CD11b-, ERK 1/2-, p38 MAP kinase- and SOCE-dependent

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...

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Veröffentlicht in:Veterinary research (Paris) 2015-03, Vol.46 (1), p.23-23
Hauptverfasser: Muñoz-Caro, Tamara, Mena Huertas, Sandra Jaqueline, Conejeros, Ivan, Alarcón, Pablo, Hidalgo, María A, Burgos, Rafael A, Hermosilla, Carlos, Taubert, Anja
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container_issue 1
container_start_page 23
container_title Veterinary research (Paris)
container_volume 46
creator Muñoz-Caro, Tamara
Mena Huertas, Sandra Jaqueline
Conejeros, Ivan
Alarcón, Pablo
Hidalgo, María A
Burgos, Rafael A
Hermosilla, Carlos
Taubert, Anja
description 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 Ca²⁺-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.
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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 Ca²⁺-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.</abstract><cop>England</cop><pub>Springer-Verlag</pub><pmid>25885264</pmid><doi>10.1186/s13567-015-0155-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Springer Nature - Complete Springer Journals; PubMed Central; Springer Nature OA/Free Journals
subjects Animals
calcium
Cattle
Cattle Diseases - immunology
Cattle Diseases - parasitology
Coccidiosis - immunology
Coccidiosis - parasitology
Coccidiosis - veterinary
Eimeria - immunology
Eimeria - ultrastructure
Eimeria bovis
elastase
Extracellular Traps - immunology
gelatinase B
granules
host specificity
Immunity, Innate
industry
Life Sciences
Microscopy, Electron, Scanning - veterinary
Microscopy, Fluorescence - veterinary
mitogen-activated protein kinase
myeloperoxidase
NADP (coenzyme)
neutrophils
Neutrophils - immunology
parasites
phosphorylation
signal transduction
Sporozoites - immunology
Sporozoites - ultrastructure
title Eimeria bovis-triggered neutrophil extracellular trap formation is CD11b-, ERK 1/2-, p38 MAP kinase- and SOCE-dependent
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