AUTHOR=Ramírez-Toloza Galia , Abello Paula , Ferreira Arturo 

TITLE=Is the Antitumor Property of Trypanosoma cruzi Infection Mediated by Its Calreticulin?

JOURNAL=Frontiers in Immunology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00268

DOI=10.3389/fimmu.2016.00268

ISSN=1664-3224

ABSTRACT=<p>Eight to 10 million people in 21 endemic countries are infected with <italic>Trypanosoma cruzi</italic>. However, only 30% of those infected develop symptoms of Chagas’ disease, a chronic, neglected tropical disease worldwide. Similar to other pathogens, <italic>T. cruzi</italic> has evolved to resist the host immune response. Studies, performed 80 years ago in the Soviet Union, proposed that <italic>T. cruzi</italic> infects tumor cells with similar capacity to that displayed for target tissues such as cardiac, aortic, or digestive. An antagonistic relationship between <italic>T. cruzi</italic> infection and cancer development was also proposed, but the molecular mechanisms involved have remained largely unknown. Probably, a variety of <italic>T. cruzi</italic> molecules is involved. This review focuses on how <italic>T. cruzi</italic> calreticulin (TcCRT), exteriorized from the endoplasmic reticulum, targets the first classical complement component C1 and negatively regulates the classical complement activation cascade, promoting parasite infectivity. We propose that this C1-dependent TcCRT-mediated virulence is critical to explain, at least an important part, of the parasite capacity to inhibit tumor development. We will discuss how TcCRT, by directly interacting with venous and arterial endothelial cells, inhibits angiogenesis and tumor growth. Thus, these TcCRT functions not only illustrate <italic>T. cruzi</italic> interactions with the host immune defensive strategies, but also illustrate a possible co-evolutionary adaptation to privilege a prolonged interaction with its host.</p>