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EQUINE VETERINARY EDUCATION


Equine vet. Educ. (2020) 32 (11) 590-602 doi: 10.1111/eve.13262


Review Article Eosinophils of the horse: Part II: Eosinophils in clinical diseases


M. M. Brosnahan* College of Veterinary Medicine, Midwestern University, Glendale, Arizona, USA *Corresponding author email: mbrosn@midwestern.edu


Keywords: horse; eosinophil; immunology; leukocyte


Summary Interpretation of eosinophilia in body fluids or tissues is often not straightforward. Eosinophil counts vary among clinically healthy individuals, and considerable overlap can occur between normal and affected animals in conditions such as allergic airway disease. Parasite exposure is a confounding factor when counts are increased, and in cases where very high counts and dramatic clinical signs make another disease process obvious, the underlying pathology may be uncertain and treatment difficult. Eosinophils are a component of the immune response in many diseases of the horse, but their specific role is often unknown and likely multifactorial. In helminth infections, eosinophils are assumed to be part of the normal host response to a pathogen, whereas in multisystemic eosinophilic epitheliotropic disease (MEED), the predominance of eosinophils likely represents a wildly dysregulated response, or an abnormal response altogether. This distinction is still not clear for other diseases. Understanding the pathways involved in recruitment, activation or suppression of eosinophils is required for more accurate diagnostics, effective therapeutics, and successful strategies for prevention of eosinophil associated diseases. Eosinophils of the horse: Part II reviews published observations on the eosinophil in clinical diseases of the horse. The behaviour of eosinophils in three common and relatively well- studied conditions is presented first, including gastrointestinal helminth infections, non-infectious respiratory disease, and insect bite hypersensitivity. The less common eosinophil- associated diseases such as eosinophilic disease confined to the intestine (EDCI) and MEED are considered, followed by a brief summary of the eosinophil in phycomycosis and neoplasia. In conclusion, a panoramic view of the equine eosinophil as presented in Parts I and II is placed in the larger context of current eosinophil research, and areas of study are identified that may improve our understanding of eosinophil biology in equine health and clinical disease.


Introduction


Eosinophils traditionally were viewed as end-effector cells in helminth infections, a paradigm that still confounds the clinical interpretation of eosinophilia. Their role in noninfectious respiratory disease and other hypersensitivities was appreciated early on, and eosinophilic responses to various pathogens have now been identified (Rothenberg and Hogan 2006; Blanchard and Rothenberg 2009; Ravin and Loy 2016; McBrien and Menzies-Gow 2017). The less common ‘eosinophil-associated diseases’, in which the eosinophil plays a critical but indeterminate role, remain poorly understood (Bochner et al. 2012). Horses suffer from illnesses in all of these categories, and veterinarians have documented associated


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changes in peripheral blood, body fluid and tissue eosinophils in natural and experimental disease. Eosinophils are involved in homeostatic pathways in other species (Marichal et al. 2017), but these have not been investigated in the horse. The objectives of Eosinophils of the horse: Part II are to review existing observations on eosinophils in clinical diseases, to interpret in the context of Part I (Brosnahan 2020) and research in other species, and to identify the salient research questions that will further our understanding of the eosinophil in equine health and disease.


Helminth infections


A role for eosinophils in the defence against helminths was proposed in the early twentieth century (Klion and Nutman 2004). Parasites initiate a Th2 response at sites of invasion, characterised by interleukin-4, interleukin-5, interleukin-9, interleukin-10 and interleukin-13, along with IgE. Mast cells and eosinophils are recruited, and granulomas are formed at sites of parasite migration. Granulomas may be extensive, located throughout the omentum and viscera including the liver, pancreas, colon, caecum and lungs (McCraw and Slocombe 1974, 1978; Petty et al. 1992; MacDonald et al. 2002; Ravin and Loy 2016). Responses vary contingent upon host and parasite species, with eosinophils sometimes facilitating rather than inhibiting parasite survival, as occurs with some stages of Trichinella spiralis in laboratory models (Huang and Appleton 2016). Eosinophils occur in association with numerous internal and external parasites of the horse (Nansen et al. 1975; MacKay and Urquhart 1979; George et al. 1981; Potter and Leid 1986; Cogley 1989; Mohamed et al. 1989; Soule et al. 1989; Hill et al. 2007; Wilford et al. 2013; Raftery et al. 2017; Zoll et al. 2018) such as Habronema spp., which primarily inhabit the equine stomach but also may cause eosinophil-replete lesions in wounds and at mucocutaneous junctions (Mohamed et al. 1989) (Fig 1). Clinically relevant gastrointestinal helminth infections are the most intensively researched.


Gastrointestinal parasites of the horse Gastrointestinal helminths are a widespread and well-studied problem in the horse. Clinical disease is associated historically with migratory large strongyles (Strongylus vulgaris, S. edentatus, S. equinus), small strongyles (cyathostomes), tapeworms (Anoplocephala perfoliata) and, in foals, ascarids (Parascarus equorum). Early studies sought to define parasite life cycles, but post-infection necropsies also described the eosinophilic response (Duncan and Pirie 1975). Host immunity and anthelmintics were the focus of later works (Bailey et al. 1989; Steuer et al. 2018). Variables exist across studies, including dosing variations, natural versus experimental


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