MCT-Dependent ICryptosporidium parvum/I-Induced Bovine Monocyte Extracellular Traps under Physioxia

• Published in: Biology (Basel, Switzerland) Switzerland), 2023-07, Vol.12 (7)
• Main Authors: Hasheminasab, Seyed Sajjad, Conejeros, Iván, Gärtner, Ulrich, Kamena, Faustin, Taubert, Anja, Hermosilla, Carlos R
• Format: Article
• Language: English
• Subjects: BCG; BCG vaccines; Developing countries; Ethylenediaminetetraacetic acid; Infection; Pharmaceutical industry; Scientific equipment and supplies industry
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12070961

Cryptosporidium parvum is a zoonotic apicomplexan parasite causing severe enteritis with high morbidity and mortality in young children, immunosuppressed patients, and newborn calves. Monocytes are bone marrow-derived myeloid leukocytes with a central role in early host innate immunity to infections and injury. Monocytes sense invasive pathogens, phagocytose, secrete cytokines/chemokines, present antigens to T cells, and release monocyte extracellular traps (METs). This study aimed to investigate the involvement of ATP purinergic receptor P2X1, glycolysis, monocarboxylate transporters (MCT), and Notch signaling in METs of bovine monocytes exposed to C. parvum. C. parvum-induced METosis was investigated under different oxygen conditions, including intestinal physioxia (5% O[sub.2]) and hyperoxia (21% O[sub.2]). C. parvum-oocysts, as well as sporozoites, robustly induced METosis and MET-associated anti-parasitic molecules such as myeloperoxidase (MPO) and histones confirmed METs extrusion. The apicomplexan protozoan parasite Cryptosporidium parvum is responsible for cryptosporidiosis, which is a zoonotic intestinal illness that affects newborn cattle, wild animals, and people all over the world. Mammalian monocytes are bone marrow-derived myeloid leukocytes with important defense effector functions in early host innate immunity due to their ATP purinergic-, CD14- and CD16-receptors, adhesion, migration and phagocytosis capacities, inflammatory, and anti-parasitic properties. The formation of monocyte extracellular traps (METs) has recently been reported as an additional effector mechanism against apicomplexan parasites. Nonetheless, nothing is known in the literature on METs extrusion neither towards C. parvum-oocysts nor sporozoites. Herein, ATP purinergic receptor P2X1, glycolysis, Notch signaling, and lactate monocarboxylate transporters (MCT) were investigated in C. parvum-exposed bovine monocytes under intestinal physioxia (5% O[sub.2]) and hyperoxia (21% O[sub.2]; most commonly used hyperoxic laboratory conditions). C. parvum-triggered suicidal METs were confirmed by complete rupture of exposed monocytes, co-localization of extracellular DNA with myeloperoxidase (MPO) and histones (H1-H4) via immunofluorescence- and confocal microscopy analyses. C. parvum-induced suicidal METs resulted not only in oocyst entrapment but also in hindered sporozoite mobility from oocysts according to scanning electron microscopy (SEM) analyses. Early parasite-induced bovi