University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medicine, Dentistry & Health Sciences Collected Works
  • Medicine, Dentistry & Health Sciences Collected Works - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Medicine, Dentistry & Health Sciences Collected Works
  • Medicine, Dentistry & Health Sciences Collected Works - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Serine Protease(s) Secreted by the Nematode Trichuris muris Degrade the Mucus Barrier

    Thumbnail
    Download
    Published version (1.011Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    63
    52
    Author
    Hasnain, SZ; McGuckin, MA; Grencis, RK; Thornton, DJ
    Date
    2012-10-01
    Source Title
    PLoS Neglected Tropical Diseases
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    McGuckin, Michael
    Affiliation
    Medicine Dentistry & Health Sciences
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Hasnain, S. Z., McGuckin, M. A., Grencis, R. K. & Thornton, D. J. (2012). Serine Protease(s) Secreted by the Nematode Trichuris muris Degrade the Mucus Barrier. PLOS NEGLECTED TROPICAL DISEASES, 6 (10), https://doi.org/10.1371/journal.pntd.0001856.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255562
    DOI
    10.1371/journal.pntd.0001856
    Abstract
    The polymeric mucin component of the intestinal mucus barrier changes during nematode infection to provide not only physical protection but also to directly affect pathogenic nematodes and aid expulsion. Despite this, the direct interaction of the nematodes with the mucins and the mucus barrier has not previously been addressed. We used the well-established Trichuris muris nematode model to investigate the effect on mucins of the complex mixture of immunogenic proteins secreted by the nematode called excretory/secretory products (ESPs). Different regimes of T. muris infection were used to simulate chronic (low dose) or acute (high dose) infection. Mucus/mucins isolated from mice and from the human intestinal cell line, LS174T, were treated with ESPs. We demonstrate that serine protease(s) secreted by the nematode have the ability to change the properties of the mucus barrier, making it more porous by degrading the mucin component of the mucus gel. Specifically, the serine protease(s) acted on the N-terminal polymerising domain of the major intestinal mucin Muc2, resulting in depolymerisation of Muc2 polymers. Importantly, the respiratory/gastric mucin Muc5ac, which is induced in the intestine and is critical for worm expulsion, was protected from the depolymerising effect exerted by ESPs. Furthermore, serine protease inhibitors (Serpins) which may protect the mucins, in particular Muc2, from depolymerisation, were highly expressed in mice resistant to chronic infection. Thus, we demonstrate that nematodes secrete serine protease(s) to degrade mucins within the mucus barrier, which may modify the niche of the parasite to prevent clearance from the host or facilitate efficient mating and egg laying from the posterior end of the parasite that is in intimate contact with the mucus barrier. However, during a T(H)2-mediated worm expulsion response, serpins, Muc5ac and increased levels of Muc2 protect the barrier from degradation by the nematode secreted protease(s).

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Medicine, Dentistry & Health Sciences Collected Works - Research Publications [578]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors