title: Eimeria ninakohlyakimovae induces NADPH oxidase-dependent monocyte extracellular trap formation and upregulates IL-12 and TNF-α, IL-6 and CCL2 gene transcription.
abstract: Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats.
authors: Parasitology Unit, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors: D
authors: D
authors: Pérez
authors: Parasitology Unit, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors: M C
authors: MC
authors: Muñoz
authors: Parasitology Unit, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors: J M
authors: JM
authors: Molina
authors: Institute of Parasitology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Giessen, Germany.
authors: T
authors: T
authors: Muñoz-Caro
authors: Institute of Parasitology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Giessen, Germany.
authors: L M R
authors: LM
authors: Silva
authors: Institute of Parasitology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Giessen, Germany.
authors: A
authors: A
authors: Taubert
authors: Institute of Parasitology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Giessen, Germany.
authors: C
authors: C
authors: Hermosilla
authors: Parasitology Unit, Department of Animal Pathology, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Las Palmas, Spain. Electronic address: antonio.ruiz@ulpgc.es.
authors: A
authors: A
authors: Ruiz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004539:Eimeria / Q000145:classification*; D005786:Gene Expression Regulation / Q000276:immunology*; D015511:Goat Diseases / Q000469:parasitology; D006041:Goats; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000502:physiology* / Q000648:ultrastructure; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D019255:NADPH Oxidases
keywords: Chemokines; Cytokines; Eimeria ninakohlyakimovae; Extracellular traps; Innate immune reactions; Monocyte