Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies.
| Title: | 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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| Authors: | Bhat SA; School of Health & Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.; Animal and Bioscience Research Department, Teagasc, Grange, Ireland.; Walton SF; School of Health & Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.; Ventura T; Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.; Liu X; School of Health & Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.; Cancer Research Institute, The First People's Hospital of Foshan, Foshan, Guangdong, China.; McCarthy JS; Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.; Burgess STG; Diagnostics, Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, United Kingdom.; Mounsey KE; School of Health & Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia. |
| Source: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2020 Sep 04; Vol. 14 (9), pp. e0008601. Date of Electronic Publication: 2020 Sep 04 (Print Publication: 2020). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science |
| MeSH Terms: | Host-Parasite Interactions/*immunology ; Sarcoptes scabiei/*immunology ; Scabies/*veterinary ; Sus scrofa/*immunology ; Sus scrofa/*parasitology; Cytokines/genetics ; Cytokines/immunology ; Gene Expression Regulation/genetics ; Immunomodulation/immunology ; Scabies/immunology ; Scabies/pathology ; Skin/immunology ; Skin/parasitology ; Skin/pathology ; Swine Diseases/immunology ; Swine Diseases/parasitology ; Th17 Cells/immunology ; Th2 Cells/immunology ; Transcriptome/genetics ; Animals ; Gene Expression Profiling ; Swine |
| 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. |
| Competing Interests: | The authors have declared that no competing interests exist. |
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| Substance Nomenclature: | 0 (Cytokines) |
| Entry Date(s): | Date Created: 20200904 Date Completed: 20201028 Latest Revision: 20201028 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7508399 |
| DOI: | 10.1371/journal.pntd.0008601 |
| PMID: | 32886659 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't