Scabies mite inactivated serine protease paralogs inhibit the human complement system

Bergstrom, Frida C., Reynolds, Simone, Johnstone, Masego, Pike, Robert N., Buckle, Ashley M., Kemp, David J., Fischer, Katja and Blom, Anna M. (2009) Scabies mite inactivated serine protease paralogs inhibit the human complement system. Journal of Immunology, 182 12: 7809-7817. doi:10.4049/jimmunol.0804205

Author Bergstrom, Frida C.
Reynolds, Simone
Johnstone, Masego
Pike, Robert N.
Buckle, Ashley M.
Kemp, David J.
Fischer, Katja
Blom, Anna M.
Title Scabies mite inactivated serine protease paralogs inhibit the human complement system
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2009-06-15
Sub-type Article (original research)
DOI 10.4049/jimmunol.0804205
Open Access Status DOI
Volume 182
Issue 12
Start page 7809
End page 7817
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Veterinary Science Publications
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Citation counts: TR Web of Science Citation Count  Cited 47 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 17:59:37 EST by Mr Andrew Martlew on behalf of School of Veterinary Science