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Clin Exp Immunol. 2019 Oct 8. doi: 10.1111/cei.13379. [Epub ahead of print]

Trypanosoma cruzi cleaves galectin-3 N-terminal domain to suppress its innate microbicidal activity.

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Centro de Biología Molecular "Severo Ochoa", Universidad Autónoma de Madrid, Nicolás Cabrera 1, Madrid, 28049, Spain.
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G128TA.


Galectin-3 is the best characterized member of galectins, an evolutionary conserved family of galactosides-binding proteins that play central roles in infection and immunity, regulating inflammation, cell migration, and cell apoptosis. Differentially expressed by cells and tissues with immune privilege, they bind not only to host ligands, but also to glycans expressed by pathogens. In this regard, we have previously shown that human galectin-3 recognizes several genetic lineages of the protozoan parasite Trypanosoma cruzi, the causal agent of Chagas´ disease or American trypanosomiasis. Herein we describe a molecular mechanism developed by T. cruzi to proteolytically process galectin-3 that generates a truncated form of the protein lacking its N-terminal domain - required for protein oligomerization - but still conserves a functional carbohydrate recognition domain (CRD). Such processing relies on specific T. cruzi proteases, including Zn-metalloproteases and collagenases, and ultimately conveys profound changes in galectin-3-dependent effects, as chemical inhibition of parasite proteases allows galectin-3 to induce parasite death in vitro. Thus, T. cruzi might have established distinct mechanisms to counteract galectin-3-mediated immunity and microbicide properties. Interestingly, non-pathogenic T. rangeli lacked the ability to cleave galectin-3 suggesting that during evolution, two genetically similar organisms have developed different molecular mechanisms, that in the case of T. cruzi, favored its pathogenicity, highlighting the importance of T. cruzi proteases to avoid immune mechanisms triggered by galectin-3 upon infection. This study provides the first evidence of a novel strategy developed by T. cruzi to abrogate signaling mechanisms associated to galectin-3-dependent innate immunity.


Chagas disease; Trypanosoma cruzi; galectin-3; innate immunity


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