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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

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Author(s):
Maeda, Fernando Yukio [1] ; Cortez, Cristian [1] ; Izidoro, Mario Augusto [2] ; Juliano, Luiz [2] ; Yoshida, Nobuko [1]
Total Authors: 5
Affiliation:
[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Infection and Immunity; v. 82, n. 12, p. 5166-5174, DEC 2014.
Web of Science Citations: 6
Abstract

Trypanosoma cruzi, the agent of Chagas disease, binds to diverse extracellular matrix proteins. Such an ability prevails in the parasite forms that circulate in the bloodstream and contributes to host cell invasion. Whether this also applies to the insect-stage metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, is not clear. Using T. cruzi CL strain metacyclic forms, we investigated whether fibronectin bound to the parasites and affected target cell invasion. Fibronectin present in cell culture medium bound to metacyclic forms and was digested by cruzipain, the major T. cruzi cysteine proteinase. G strain, with negligible cruzipain activity, displayed a minimal fibronectin-degrading effect. Binding to fibronectin was mediated by gp82, the metacyclic stage-specific surface molecule implicated in parasite internalization. When exogenous fibronectin was present at concentrations higher than cruzipain can properly digest, or fibronectin expression was stimulated by treatment of epithelial HeLa cells with transforming growth factor beta, the parasite invasion was reduced. Treatment of HeLa cells with purified recombinant cruzipain increased parasite internalization, whereas the treatment of parasites with cysteine proteinase inhibitor had the opposite effect. Metacyclic trypomastigote entry into HeLa cells was not affected by anti-beta 1 integrin antibody but was inhibited by anti-fibronectin antibody. Overall, our results have indicated that the cysteine proteinase of T. cruzi metacyclic forms, through its fibronectin-degrading activity, is implicated in host cell invasion. (AU)

FAPESP's process: 11/51475-3 - Molecular and cellular biology of the parasitism by Trypanosoma cruzi
Grantee:José Franco da Silveira Filho
Support Opportunities: Research Projects - Thematic Grants