Abstract
Background: Crusted scabies is a severe manifestation of Sarcoptes scabiei infection, akin to chronic mange in animals. Detailed understanding of scabies immunopathology is lacking, with research impeded by sporadic access to patients and the inability to undertake longitudinal study of infection in humans. We have responded to this by developing a tractable porcine model of human scabies. Pigs are a natural host of scabies, and show similar clinical and, immunological changes to humans, including susceptibility to hyperinfection that resembles human crusted scabies. In previous work, we established a porcine model of crusted scabies using the glucocorticoid dexamethasone. In this study, we report the temporal development of scabies immunopathology in different disease phenotypes. Methods: We completed a 24-week trial involving four treatment groups. Pigs were scored for lesion development and parasite burden, and skin biopsies collected for parallel histologic studies. qRT-PCR was undertaken to assess transcriptional levels of key Th1, Th2, and Th17 cytokines across the trial. Results: A range of different clinical phenotypes of scabies was observed. qRT-PCR analysis confirmed an association between disease severity and transcription levels of the Th2 cytokines IL-4 and IL-13, which were significantly increased at weeks 4, 8 and 12 post infection. Interestingly, we also saw significant and differential up-regulation of the Th17 cytokines IL-17 and IL-23 in pigs with crusted scabies. In contrast, no significant changes in IL-10 or IFN-γ transcription were observed. Conclusions: We observed an association between crusted scabies and a dysregulated immune response involving increased Th2, IL-17 and IL-23 cytokine transcription. Development of an informative animal model represents a breakthrough in scabies research, establishing the foundation for prospective studies of the dermal immunopathology of scabies. Describing the skin pathogenesis of scabies in detail is essential for the future design of immunotherapeutics for this disease. This may lead to strategies to protect vulnerable subjects from contracting crusted scabies, and will ultimately result in improved skin health for disadvantaged communities and better management of scabies in veterinary settings.