A Panoramic View of the Immune Response to Trypanosoma cruzi Infection

The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

“…This IFN- γ peak might be key in the control of the infection during the acute phase of Chagas disease, as the depletion of NK cells from those mice causes an abrogation in IFN- γ production and an increase in IL-10 levels, which probably leads to tolerance of the parasite and allows infection progression [ 77 ]. In addition, NK cells can directly eliminate extracellular parasites by forming intercellular contacts with the pathogen cell, which results in the loss of motility and damage in the cell membrane of the parasite [ 66 , 78 , 79 ]. This killing activity of the NK cells depends on activation by IL-12 and results in the exocytosis of cytotoxic granules, which can damage the cell membrane of the parasite [ 66 , 78 , 79 ].…”

“…In addition, NK cells can directly eliminate extracellular parasites by forming intercellular contacts with the pathogen cell, which results in the loss of motility and damage in the cell membrane of the parasite [ 66 , 78 , 79 ]. This killing activity of the NK cells depends on activation by IL-12 and results in the exocytosis of cytotoxic granules, which can damage the cell membrane of the parasite [ 66 , 78 , 79 ]. It is believed that NK cell primary function is the direct killing of the parasite, more than the elimination of T. cruzi -infected cells [ 66 , 79 ].…”

“…This killing activity of the NK cells depends on activation by IL-12 and results in the exocytosis of cytotoxic granules, which can damage the cell membrane of the parasite [ 66 , 78 , 79 ]. It is believed that NK cell primary function is the direct killing of the parasite, more than the elimination of T. cruzi -infected cells [ 66 , 79 ]. It is noteworthy to mention that expression of genes related to NK cell's function is upregulated in PCR-positive asymptomatic patients with Chagas disease, while they are downregulated in those patients with severe cardiomyopathy [ 80 ].…”

“…It consists of several plasmatic proteins, which are able to opsonize pathogens, recruit phagocytes to the infection site, and also directly destroy the invading pathogen [ 66 ]. It functions as a cascade of proteolytic enzymes, in which a precursor (zymogen) is activated turning it up in an active proteolytic enzyme able to cleave and activate the following component [ 66 , 79 ]. The complement system works by amplifying the signal generated by the presence of the pathogen to allow the clearance of the invading pathogen.…”

“…However, despite the power of the complement system to control initial infections, T. cruzi has evolved a myriad of molecules to escape or subvert the complement system, by either inactivation or blocking the activation of its components. For example, calreticulin (TcCRT) is a T. cruzi endoplasmic reticulum protein, which is translocated to the surface upon infection, and it has been demonstrated that it can bind to several molecular pattern sensors, such as C1q, mannose binding lectin, and L-ficolin [ 66 , 79 , 82 ], thereby affecting the first step on the classical and lectin complement system pathway. Several other examples of complement system inactivation by T. cruzi molecules can be found in Reference [ 66 , 79 ].…”