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

Mohlin, Frida LU ; Reynolds, Simone; Johnstone, Masego; Pike, Robert N; Buckle, Ashley M; Kemp, David J; Fischer, Katja and Blom, Anna LU (2009) In Journal of immunology (Baltimore, Md. : 1950) 182(12). p.7809-7817
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Serine Endopeptidases: isolation & purification, Serine Endopeptidases: genetics, Scabies: pathology, Scabies: immunology, Complement System Proteins: immunology, Sarcoptes scabiei: enzymology, Serine Endopeptidases: metabolism
in
Journal of immunology (Baltimore, Md. : 1950)
volume
182
issue
12
pages
7809 - 7817
publisher
American Association of Immunologists
external identifiers
  • WOS:000266833900052
  • PMID:19494305
  • Scopus:67649160597
ISSN
1550-6606
DOI
10.4049/jimmunol.0804205
language
English
LU publication?
yes
id
b84d6a6e-d2e5-4539-a985-7a26807f6de8 (old id 1434539)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19494305?dopt=Abstract
date added to LUP
2009-07-02 13:03:25
date last changed
2016-11-01 10:16:41
@misc{b84d6a6e-d2e5-4539-a985-7a26807f6de8,
  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.},
  author       = {Mohlin, Frida and Reynolds, Simone and Johnstone, Masego and Pike, Robert N and Buckle, Ashley M and Kemp, David J and Fischer, Katja and Blom, Anna},
  issn         = {1550-6606},
  keyword      = {Serine Endopeptidases: isolation & purification,Serine Endopeptidases: genetics,Scabies: pathology,Scabies: immunology,Complement System Proteins: immunology,Sarcoptes scabiei: enzymology,Serine Endopeptidases: metabolism},
  language     = {eng},
  number       = {12},
  pages        = {7809--7817},
  publisher    = {ARRAY(0xa74f9e0)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Scabies mite inactivated serine protease paralogs inhibit the human complement system.},
  url          = {http://dx.doi.org/10.4049/jimmunol.0804205},
  volume       = {182},
  year         = {2009},
}