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Trypanosoma cruzi and its gp83 ligand modulate host thrombospondin 1 and laminin γ‐1 gene networks to recruit trypanosomes in the early infection process
Author(s) -
Nde Pius,
Cardenas Tatiana C,
Johnson Candice A,
Pratap Siddharth,
Kleshchenko Yulia Y,
Furtak Vyachslav A,
Lima Maria F,
Villalta Fernando
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.480.7
Subject(s) - trypanosoma cruzi , laminin , biology , thrombospondin , gene silencing , extracellular matrix , microbiology and biotechnology , extracellular , chagas disease , gene , immunology , metalloproteinase , parasite hosting , genetics , matrix metalloproteinase , world wide web , computer science
Trypanosoma cruzi, the protozoan that causes Chagas heart disease, uses the extracellular matrix to facilitate infection of human cells. However, the mechanisms underlying this process are unknown. Here we show that T. cruzi gp83 ligand, a GPI‐anchored molecule that the parasite uses to attach to host cells, is cleaved by the trypanosome PLC. The cleaved gp83 signals the host cell to increase laminin γ‐1 expression to facilitate the initial recruitment of trypanosomes to the extracellular matrix. Then, the recruited trypanosomes up‐regulate the expression of thrombospondin 1 (TSP1), which also enhances the initial infection process. The over‐expression of laminin γ‐1 and TSP1 in cells enhances trypanosome infection whereas silencing of laminin γ‐1 and TSP1 significantly reduces the trypanosome infection. We have determined the laminin γ‐1 and TSP1 specific gene networks that interact within the human protein interactome during the early infection process. We conclude that T. cruzi uses different strategies to manipulate the extracellular matrix to facilitate the initial infection process (Supported by NIH grants AI080580‐03, AI007281‐21 and AI083925‐01).