Abstract
Scabies, a human skin infestation caused by the ectoparasitic mite Sarcoptes scabiei var. hominis, affects more than 200 million people globally. The prevailing knowledge of the disease process and host immune response mechanisms is limited. A better understanding of the host-parasite relationship is essential for the identification of novel vaccine and drug targets. Here we aimed to interrogate the transcriptomic profiles of mite-infested human skin biopsies with clinical manifestations of ordinary scabies subjects (“OS”; n = 05) and subjects naive to scabies (“control”; n = 03) using RNASeq data analysis. A combined clustering, network, and pathway mapping approach enabled us to identify key signaling events in the host immune and pro-inflammatory responses to S. scabiei infestation. The clustering patterns showed various differentially expressed genes including inflammatory responses and innate immunity genes (DEFB4A, IL-19, CXCL8, CSF3, SERPINB4, S100A7A, HRNR) and notably upregulation of the JAK-STAT pathway in scabies-infested samples. Mite-infested human skin biopsies (GSE178563) were compared with an ex-vivo porcine infested model (E-MTAB-6433) and human skin equivalents (GSE48459). Marked enrichment of immune response pathways (JAK-STAT signaling, IL-4 and IL-13 pathway, and Toll receptor cascade), chemokine ligands and receptors (CCL17, CCL18, CCL3L1, CCL3L3, CCR7), and cytokines (IL-13 and IL-20) were observed. Additionally, genes known for their role in psoriasis and atopic dermatitis were upregulated, e.g., IL-19. The detailed transcriptomic profile has provided an insight into molecular functions, biological processes, and immunological responses and increased our understanding about transcriptomic regulation of scabies in human.
Highlights
Scabies is a common contagious human skin infestation caused by ectoparasite Sarcoptes scabiei var. hominis (S. scabiei var. hominis) [1, 2]
The skin biopsies of three naïve individuals with no history of skin allergy were included in the analysis as controls to avoid any confounding in inflammatory host immune responses and allow data comparison and interpretation with the porcine model
RNA extracted from all eight skin biopsy samples showed a good RNA integrity (RIN) value ranging between 7.6 to 8.6 (Supplementary Figure 1)
Summary
Scabies is a common contagious human skin infestation caused by ectoparasite Sarcoptes scabiei var. hominis (S. scabiei var. hominis) [1, 2]. Scabies is a common contagious human skin infestation caused by ectoparasite Sarcoptes scabiei var. Infestation by the mite almost always leads to the development of localized skin inflammation, itching, and burrow formation; rash and itch possibly being an indicator of host immune response with features of both type I and type IV hypersensitivity reactions [6]. The initial immune response towards the mite and its products, by different hosts, consists of keratinocytes, neutrophils, Langerhans cells, and macrophages [7, 8], which initiate an inflammatory and immune reaction [9]. In a study reported by Walton et al in 2008, skin biopsies taken from scabies patients having crusted lesions showed large numbers of lymphocytes, monocytes, macrophages, and eosinophils in the dermis, with increased levels of IgE in the blood samples. Similar findings have been reported in the skin, upper airways, and lung cellular infiltrates present in chronic allergic inflammation [11]
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