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

Kate Mounsey, Hugh Murray, Helle Bielefeldt-Ohmann, Cielo Pasay, Deborah Holt, Bart Currie, Shelley Faye Walton, James McCarthy

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    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.
    Original languageEnglish
    Article numbere0003498
    Pages (from-to)1-17
    Number of pages17
    JournalPLoS Neglected Tropical Diseases
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 2015

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    Sarcoptes scabiei
    Scabies
    Critical Pathways
    Swine
    Prospective Studies
    Dexamethasone
    Interleukin-17
    Cytokines
    Interleukin-23
    Interleukin-13
    Mast Cells
    Interleukin-4
    Glucocorticoids
    Longitudinal Studies

    Cite this

    Mounsey, Kate ; Murray, Hugh ; Bielefeldt-Ohmann, Helle ; Pasay, Cielo ; Holt, Deborah ; Currie, Bart ; Walton, Shelley Faye ; McCarthy, James. / Prospective study in a porcine model of Sarcoptes scabiei indicates the association of Th2 and Th17 pathways with the clinical severity of scabies. In: PLoS Neglected Tropical Diseases. 2015 ; Vol. 9, No. 3. pp. 1-17.
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    title = "Prospective study in a porcine model of Sarcoptes scabiei indicates the association of Th2 and Th17 pathways with the clinical severity of scabies",
    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.",
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    author = "Kate Mounsey and Hugh Murray and Helle Bielefeldt-Ohmann and Cielo Pasay and Deborah Holt and Bart Currie and Walton, {Shelley Faye} and James McCarthy",
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    Prospective study in a porcine model of Sarcoptes scabiei indicates the association of Th2 and Th17 pathways with the clinical severity of scabies. / Mounsey, Kate; Murray, Hugh; Bielefeldt-Ohmann, Helle; Pasay, Cielo; Holt, Deborah; Currie, Bart; Walton, Shelley Faye; McCarthy, James.

    In: PLoS Neglected Tropical Diseases, Vol. 9, No. 3, e0003498 , 2015, p. 1-17.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Prospective study in a porcine model of Sarcoptes scabiei indicates the association of Th2 and Th17 pathways with the clinical severity of scabies

    AU - Mounsey, Kate

    AU - Murray, Hugh

    AU - Bielefeldt-Ohmann, Helle

    AU - Pasay, Cielo

    AU - Holt, Deborah

    AU - Currie, Bart

    AU - Walton, Shelley Faye

    AU - McCarthy, James

    PY - 2015

    Y1 - 2015

    N2 - 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.

    AB - 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.

    KW - CD3 antigen

    KW - gamma interferon

    KW - hypoxanthine phosphoribosyltransferase

    KW - interleukin 10

    KW - interleukin 13

    KW - interleukin 17

    KW - interleukin 2

    KW - interleukin 23

    KW - interleukin 4

    KW - interleukin 5

    KW - interleukin 6

    KW - transforming growth factor beta

    KW - cytokine

    KW - dexamethasone

    KW - animal experiment

    KW - animal model

    KW - animal tissue

    KW - antibody labeling

    KW - Article

    KW - disease association

    KW - disease severity

    KW - female

    KW - histology

    KW - immunohistochemistry

    KW - immunopathology

    KW - lymphocytic infiltration

    KW - nonhuman

    KW - pig

    KW - polymerase chain reaction

    KW - porcine model

    KW - prospective study

    KW - reverse transcription

    KW - Sarcoptes scabiei

    KW - scabies

    KW - skin biopsy

    KW - Th17 cell

    KW - Th2 cell

    KW - upregulation

    KW - animal

    KW - disease model

    KW - genetics

    KW - immunology

    KW - pathology

    KW - Animals

    KW - Antigens, CD3

    KW - Cytokines

    KW - Dexamethasone

    KW - Disease Models, Animal

    KW - Interleukin-13

    KW - Interleukin-17

    KW - Interleukin-4

    KW - Prospective Studies

    KW - Scabies

    KW - Swine

    KW - Th17 Cells

    KW - Th2 Cells

    U2 - 10.1371/journal.pntd.0003498

    DO - 10.1371/journal.pntd.0003498

    M3 - Article

    VL - 9

    SP - 1

    EP - 17

    JO - PLoS Neglected Tropical Diseases

    JF - PLoS Neglected Tropical Diseases

    SN - 1935-2727

    IS - 3

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