Prospective Study in a Porcine Model of Sarcoptes scabiei Indicates the Association of Th2 and Th17 Pathways with the Clinical Severity of Scabies

BackgroundUnderstanding 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 FindingsProspective 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/ SignificanceWhile 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

Proteins on the catwalk: modelling the structural domains of the CCN family of proteins

The CCN family of proteins (CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6) are multifunctional mosaic proteins that play keys roles in crucial areas of physiology such as angiogenesis, skeletal development tumourigenesis, cell proliferation, adhesion and survival. This expansive repertoire of functions comes through a modular structure of 4 discrete domains that act both independently and in concert. How these interactions with ligands and with neighbouring domains lead to the biological effects is still to be explored but the molecular structure of the domains is likely to play an important role in this. In this review we have highlighted some of the key features of the individual domains of CCN family of proteins based on their biological effects using a homology modelling approach

Report of the First Human Case of Caulobacter sp. Infection

A Caulobacter sp. isolate was recovered from the dialysis fluid of a patient undergoing peritoneal dialysis. Bacterial identification included electron microscopy and 16S rDNA sequencing. To our knowledge, this is the first report of human Caulobacter infection. Special growth requirements suggest that Caulobacter spp. may be overlooked in the clinical microbiology laboratory

Representative histology and immunohistochemistry of skin lesions at week 12 post infestation with <i>Sarcoptes scabiei</i>.

<p>(A) Crusted scabies, hematoxylin and eosin stain; (B) Ordinary scabies, hematoxylin and eosin stain; (C) Crusted scabies, anti-CD3+ antibody T cell stain; (D) Crusted scabies, toluidine blue mast cell stain. Scale bars = 100μM.</p

Changes in cytokine transcription in skin biopsies collected from all pigs at weeks 4, 8 and 12 post-infestation with <i>Sarcoptes scabiei</i>.

<p>Group A n = 6, B+ n = 2, B n = 4, C n = 6. qRT-PCR was performed on 1μg total RNA and transcription normalised to the housekeeping gene HPRT1. Relative fold-changes in gene transcription in treatment groups were calculated by comparison to control pigs in Group D (n = 6). * = p<0.05, ** = p<0.001, ***p<0.0001 vs control, unpaired T test. Bars represent mean +/- SEM. Abbreviations: IL, interleukin, IFN, interferon, TGF, transforming growth factor.</p

Numbers of CD3+ cells (A) and mast cells (B) in skin biopsies collected from representative pigs at week 0, 4, 8 and 12 post-infestation with <i>Sarcoptes scabiei</i>.

<p>Group A n = 2, B+ n = 2, B n = 2, C n = 2, D n = 2. Group B+ = pigs in group B that developed crusted scabies based on mite counts and lesion scores.</p

Representative IL-17 staining of skin lesion at week 12 post infestation with <i>Sarcoptes scabiei</i>.

<p>(A) Crusted scabies, (B) Ordinary scabies, (C) Non-infested, (D) anti-interleukin-17 isotype control antibody. Scale bars = 100μM.</p