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Scabies mite peritrophins are potential targets of human host innate immunity

Mika, Angela, Goh, Priscilla, Holt, Deborah C., Kemp, Dave J. and Fischer, Katja (2011). Scabies mite peritrophins are potential targets of human host innate immunity. PLoS Neglected Tropical Diseases,5(9):e1331.

Document type: Journal Article
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Title Scabies mite peritrophins are potential targets of human host innate immunity
Author Mika, Angela
Goh, Priscilla
Holt, Deborah C.
Kemp, Dave J.
Fischer, Katja
Journal Name PLoS Neglected Tropical Diseases
Publication Date 2011
Volume Number 5
Issue Number 9
ISSN 1935-2727   (check CDU catalogue open catalogue search in new window)
Start Page e1331
Total Pages 11
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DEST)
Abstract Background: Pruritic scabies lesions caused by Sarcoptes scabiei burrowing in the stratum corneum of human skin facilitate opportunistic bacterial infections. Emerging resistance to current therapeutics emphasizes the need to identify novel targets for protective intervention. We have characterized several protein families located in the mite gut as crucial factors for hostparasite interactions. Among these multiple proteins inhibit human complement, presumably to avoid complementmediated damage of gut epithelial cells. Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement.

Methodology/Principal Findings:
A novel full length scabies mite peritrophin (SsPTP1) was identified in a cDNA library from scabies mites. The amino acid sequence revealed four putative chitin binding domains (CBD). Recombinant expression of one CBD of the highly repetitive SsPTP1 sequence as TSP-hexaHis-fusion protein resulted in soluble protein, which demonstrated chitin binding activity in affinity chromatography assays. Antibodies against a recombinant SsPTP1 fragment were used to immunohistochemically localize native SsPTP1 in the mite gut and in fecal pellets within the upper epidermis, co-localizing with serum components such as host IgG and complement. Enzymatic deglycosylation confirmed strong Nand O-glycosylation of the native peritrophin. Serum incubation followed by immunoblotting with a monoclonal antibody against mannan binding lectin (MBL), the recognition molecule of the lectin pathway of human complement activation, indicated that MBL may specifically bind to glycosylated SsPTP1.

Conclusions/Significance:
This study adds a new aspect to the accumulating evidence that complement plays a major role in scabies mite biology. It identifies a novel peritrophin localized in the mite gut as a potential target of the lectin pathway of the complement cascade. These initial findings indicate a novel role of scabies mite peritrophins in triggering a host innate immune response within the mite gut.
DOI http://dx.doi.org/10.1371/journal.pntd.0001331   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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