Staphylococcus aureus proteases trigger eosinophil-mediated skin inflammation.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton's syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

Cardiac Rhabdomyoma in Four Göttingen Minipigs.

Göttingen minipigs are increasingly used as an alternative large animal model in nonclinical toxicology studies, and proliferative lesions in this species are rare. Here, we report four cases of cardiac rhabdomyoma in Göttingen minipigs, an incidental and benign mass in the heart. Three cases lacked gross observations and had a microscopic nodule in either the left ventricle or interventricular septum. The last case had a large, firm, raised nodule on a left ventricular papillary muscle noted at necropsy, with additional microscopic intramural masses in the left ventricular wall. In all cases, microscopic evaluation revealed well-circumscribed, expansile nodules composed of bundles of large, highly vacuolated, ovoid to polygonal cells with variable cytoplasmic processes radiating from a centrally located nucleus. Cells displayed patchy accumulation of intracytoplasmic, PAS-positive material and haphazardly arranged cytoplasmic cross-striations. There was no evidence of cardiac insufficiency or other data to suggest the masses were clinically meaningful. Cardiac rhabdomyomas have been reported in meat-hybrid swine, with a breed predisposition in red wattle. This lesion is well established in guinea pigs, but documentation in other laboratory species used in toxicologic studies is limited to two beagle dogs. To our knowledge, this is the first report of spontaneous cardiac rhabdomyoma in Göttingen minipigs.