Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies

Sajad A Bhat; Shelley F Walton; Tomer Ventura; Xiao Song Liu; James S McCarthy; Stewart T. G Burgess; Kate E Mounsey

doi:10.1371/journal.pntd.0008601

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Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies

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Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies

Sajad A Bhat, Shelley F Walton, Tomer Ventura, Xiao Song Liu, James S McCarthy, Stewart T. G Burgess and Kate E Mounsey

PLoS Neglected Tropical Diseases, Vol.14(9), pp.1-28

2020

DOI: https://doi.org/10.1371/journal.pntd.0008601

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Abstract

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.

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Title: Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies
Authors: Sajad A Bhat (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - Legacy
Shelley F Walton (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - Legacy
Tomer Ventura (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Xiao Song Liu (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - Legacy
James S McCarthy (Author) - QIMR Berghofer Medical Research Institute
Stewart T. G Burgess (Author) - Moredun Research Institute
Kate E Mounsey (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - Legacy
Publication details: PLoS Neglected Tropical Diseases, Vol.14(9), pp.1-28
Publisher: Public Library of Science
Date published: 2020
DOI: 10.1371/journal.pntd.0008601
ISSN: 1935-2735
Copyright note: © 2020 Bhat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Grants: A porcine model to provide new insights on scabies immunopathology, DE120101701, Australian Research Council (Australia, Canberra) - ARC
Inside the skin: Understanding different host responses in scabies, 1027434, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Organisation Unit: School of Health - Biomedicine; School of Science and Engineering - Legacy; GeneCology Research Centre - Legacy; School of Health and Sport Sciences - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99474808802621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Infectious Diseases; Parasitology; Tropical Medicine

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