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The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue

Author

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  • Roman Thibeaux

    (Institut Pasteur, Unité Biologie Cellulaire du Parasitisme
    INSERM U786)

  • Patrick Avé

    (Institut Pasteur, Unité d’Histophatologie Humaine et modèles animaux)

  • Michèle Bernier

    (Hôpital Foch, Service Anatomopathologie)

  • Marie Morcelet

    (Hôpital Foch, Service Anatomopathologie)

  • Pascal Frileux

    (Hôpital Foch, Chirurgie générale et digestive)

  • Nancy Guillén

    (Institut Pasteur, Unité Biologie Cellulaire du Parasitisme
    INSERM U786)

  • Elisabeth Labruyère

    (Institut Pasteur, Unité Biologie Cellulaire du Parasitisme
    INSERM U786)

Abstract

Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs’ proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.

Suggested Citation

  • Roman Thibeaux & Patrick Avé & Michèle Bernier & Marie Morcelet & Pascal Frileux & Nancy Guillén & Elisabeth Labruyère, 2014. "The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6142
    DOI: 10.1038/ncomms6142
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