Prospective study in a porcine model of sarcoptes scabiei indicates the association of Th2 and Th17 pathways with the clinical severity of scabies

PLoS Negl Trop Dis. 2015 Mar 2;9(3):e0003498. doi: 10.1371/journal.pntd.0003498. eCollection 2015 Mar.

Abstract

Background: Understanding of scabies immunopathology has been hampered by the inability to undertake longitudinal studies in humans. Pigs are a useful animal model for scabies, and show clinical and immunologic changes similar to those in humans. Crusted scabies can be readily established in pigs by treatment with the glucocorticoid dexamethasone (Dex).

Methodology/ principal findings: Prospective study of 24 pigs in four groups: a) Scabies+/Dex+, b) Scabies+/Dex-, c) Scabies-/Dex+ and d) Scabies-/Dex-. Clinical symptoms were monitored. Histological profiling and transcriptional analysis of skin biopsies was undertaken to compare changes in cell infiltrates and representative cytokines. A range of clinical responses to Sarcoptes scabiei were observed in Dex treated and non-immunosuppressed pigs. An association was confirmed between disease severity and transcription of the Th2 cytokines IL-4 and IL-13, and up-regulation of the Th17 cytokines IL-17 and IL-23 in pigs with crusted scabies. Immunohistochemistry revealed marked infiltration of lymphocytes and mast cells, and strong staining for IL-17.

Conclusions/ significance: While an allergic Th2 type response to scabies has been previously described, these results suggest that IL-17 related pathways may also contribute to immunopathology of crusted scabies. This may lead to new strategies to protect vulnerable subjects from contracting recurrent crusted scabies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / analysis
  • Cytokines / genetics
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Interleukin-13 / analysis
  • Interleukin-17 / analysis
  • Interleukin-4 / analysis
  • Prospective Studies
  • Scabies / immunology*
  • Scabies / pathology
  • Swine
  • Th17 Cells / immunology
  • Th2 Cells / immunology*

Substances

  • CD3 Complex
  • Cytokines
  • Interleukin-13
  • Interleukin-17
  • Interleukin-4
  • Dexamethasone

Grants and funding

This work was supported by Australian National Health and Medical Research Council (NHMRC, www.nhmrc.gov.au) Project Grants (496635, 1027434 to KEM, JSM, SFW, DCH, BJC, CP); an Australian Research Council (www.arc.gov.au) DECRA Fellowship (DE120101701 to KEM); and an NHMRC Practitioner Fellowship (1041802 to JSM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.