Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset

• Published in: PLoS pathogens Vol. 15; no. 5; p. e1007803
• Main Authors: Ono, Hisaya K, Hirose, Shouhei, Narita, Kouji, Sugiyama, Makoto, Asano, Krisana, Hu, Dong-Liang, Nakane, Akio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2019; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Biocompatibility; Biology and life sciences; Biopolymers; Callithrix; Central nervous system; Common marmoset; Degranulation; Disease Models, Animal; Emetics - toxicity; Enterotoxins; Enterotoxins - toxicity; Food contamination; Food contamination & poisoning; Food poisoning; Gastrointestinal agents; Gastrointestinal system; Gastrointestinal tract; Genomes; Health aspects; Histamine; Histamine Release - drug effects; Immunology; Influence; Intestine; Intestines - drug effects; Intestines - pathology; Mast cells; Mast Cells - drug effects; Mast Cells - metabolism; Mast Cells - pathology; Medicine and Health Sciences; Monkeys; Monkeys & apes; Motion sickness; Pharmacology; Physical Sciences; Physiological aspects; Poisoning; Primates; Reflex; Research and Analysis Methods; Risk factors; Sensory neurons; Septic shock; Serotonin; Shock; Staphylococcal enterotoxin A; Staphylococcal enterotoxin F; Staphylococcal Food Poisoning - etiology; Staphylococcal Food Poisoning - metabolism; Staphylococcal Food Poisoning - pathology; Staphylococcal Infections - metabolism; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus - pathogenicity; Staphylococcus aureus; Staphylococcus aureus infections; Toxic shock syndrome; Toxins; University graduates; Vagus nerve; Veterinary colleges; Veterinary medicine; Vomiting; Vomiting - chemically induced; Vomiting - microbiology; Zoonoses; Japan
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007803

Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are known as causative agents of emetic food poisoning. We previously demonstrated that SEA binds with submucosal mast cells and evokes mast cell degranulation in a small emetic house musk shrew model. Notably, primates have been recognized as the standard model for emetic assays and analysis of SE emetic activity. However, the mechanism involved in SEA-induced vomiting in primates has not yet been elucidated. In the present study, we established common marmosets as an emetic animal model. Common marmosets were administered classical SEs, including SEA, SEB and SEC, and exhibited multiple vomiting responses. However, a non-emetic staphylococcal superantigen, toxic shock syndrome toxin-1, did not induce emesis in these monkeys. These results indicated that the common marmoset is a useful animal model for assessing the emesis-inducing activity of SEs. Furthermore, histological analysis uncovered that SEA bound with submucosal mast cells and induced mast cell degranulation. Additionally, ex vivo and in vivo pharmacological results showed that SEA-induced histamine release plays a critical role in the vomiting response in common marmosets. The present results suggested that 5-hydroxytryptamine also plays an important role in the transmission of emetic stimulation on the afferent vagus nerve or central nervous system. We conclude that SEA induces histamine release from submucosal mast cells in the gastrointestinal tract and that histamine contributes to the SEA-induced vomiting reflex via the serotonergic nerve and/or other vagus nerve.