Bacterial Toxins Predispose the Horse’s Respiratory Tract to Equine Herpesvirus

A fascinating study that finds some respiratory bacterial pathogens produce toxins that increase the susceptibility of the equine respiratory system to infection with EHV-1. Described are the mechanisms of this increased sensitivity. The same has been found with other respiratory irritants including pollens and mycotoxins. The take home message here is that the horse’s respiratory system seems uniquely sensitive to respired irritants, toxins, and microorganisms. This emphasizes how important fresh, dust free air is to the horse, for more see, https://horseadvice.com/horse-equine/horse-care/pasture-fences-barns/barn-design-and-layout/ and for aggressive management see https://horseadvice.com/horse-equine/diseases/respiratory-system/equine-asthma-heaves-in-horses/.
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Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection
Viruses. 2022 Jan 14;14(1):149. doi: 10.3390/v14010149.
Authors
Eline Van Crombrugge 1 , Emma Vanbeylen 1 , Jolien Van Cleemput 2 , Wim Van den Broeck 3 , Kathlyn Laval 1 , Hans Nauwynck 1
Affiliations

1 Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
2 Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
3 Department of Morphology, Medical Imaging, Orthopedics and Nutrition, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.

PMID: 35062352
DOI: 10.3390/v14010149

Abstract

Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air-liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse’s sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection.

Keywords: Bordetella bronchiseptica; EHV-1; Staphylococcus aureus; adenylate cyclase toxin; cell junctions; equine respiratory mucosal explants; mucosal barriers; α-hemolysin toxin.