Structural bases that underline Trypanosoma cruzi calreticulin proinfective, antiangiogenic and antitumor properties.

Structural bases that underline Trypanosoma cruzi calreticulin proinfective, antiangiogenic and antitumor properties. Immunobiology. 2019 Nov 05;: Authors: Peña Álvarez J, Teneb J, Maldonado I, Weinberger K, Rosas C, Lemus D, Valck C, Olivera-Nappa Á, Asenjo JA, Ferreira A Abstract Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays....
Source: Immunobiology - Category: Allergy & Immunology Authors: Tags: Immunobiology Source Type: research