The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Scabies mite inactivated serine protease paralogs inhibit the human complement system.

På svenska

Author

  • Frida Mohlin
  • Simone Reynolds
  • Masego Johnstone
  • Robert N Pike
  • Ashley M Buckle
  • David J Kemp
  • Katja Fischer
  • Anna Blom

Summary, in English

Infestation of skin by the parasitic itch mite Sarcoptes scabiei afflicts 300 million people worldwide and there is a need for novel and efficient therapies. We have previously identified a multigene family of serine proteases comprising multiple catalytically inactive members (scabies mite-inactivated protease paralogs (SMIPPs)), which are secreted into the gut of S. scabiei. SMIPPs are located in the mite gut and in feces excreted into the upper epidermis. Scabies mites feed on epidermal protein, including host plasma; consequently, they are exposed to host defense mechanisms both internally and externally. We found that two recombinantly expressed SMIPPs inhibited all three pathways of the human complement system. Both SMIPPs exerted their inhibitory action due to binding of three molecules involved in the three different mechanisms which initiate complement: C1q, mannose-binding lectin, and properdin. Both SMIPPs bound to the stalk domains of C1q, possibly displacing or inhibiting C1r/C1s, which are associated with the same domain. Furthermore, we found that binding of both SMIPPs to properdin resulted in prevention of assembly of the alternative pathway convertases. However, the SMIPPs were not able to dissociate already formed convertases. Immunohistochemical staining demonstrated the presence of C1q in the gut of scabies mites in skin burrows. We propose that SMIPPs minimize complement-mediated gut damage and thus create a favorable environment for the scabies mites.

Publishing year

2009

Language

English

Pages

7809-7817

Publication/Series

Journal of immunology

Volume

182

Issue

12

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Keywords

  • Serine Endopeptidases: isolation & purification
  • Serine Endopeptidases: genetics
  • Scabies: pathology
  • Scabies: immunology
  • Complement System Proteins: immunology
  • Sarcoptes scabiei: enzymology
  • Serine Endopeptidases: metabolism

Status

Published

Research group

  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1550-6606