Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Resistance to complement lysis
Trypomastigotes must evade this powerful mechanism of killing before entry into host cells and again after they emerge. They possess membrane-bound proteins that impair complement activation, such as complement regulatory proteins (160-CRP),189 decay-accelerating factor (T-DAF),190 gp58/68,191 and calreticulin192 expressed by trypomastigotes, and a 27-32 kDa protein expressed by metacyclic trypomastigotes.193 Amastigotes resist complement lysis through a mechanism totally different from trypomastigotes.194
T. cruzi possesses a large arsenal of antioxidant enzymes allowing it to resist to the trypanocidal action of phagocytes.66 The parasite also takes advantage when low
amounts of NO are produced in resident macrophages, as it favors parasite proliferation instead of impeding it.63 Next, GIPLs and GPI-anchors rapidly induce apoptosis of resident macrophages, an effect reinforced by IFN-y. This leads to the release of amastigotes before they are killed intracellularly, which may then infect other cells.195 Moreover, amastigotes preferentially invade nonactivated macrophages, i.e., not armed to kill the parasite. This may be related to their use of the mannose receptor (MR) for entry, the expression of which is decreased on IFN-Y-activated macrophages.196 Trypomastigotes do not bind to MR, conferring to amastigotes an advantage to achieve the persistence of the infection.
Besides, cruzipain limits macrophage activation by inducing proteolysis or the transcription factor NF-kB, leading to unresponsiveness of the macrophage during early infection. This immune evasion mechanism may be critical for T. cruzi survival during early infection with a low number of trypmastigotes,197 while abundant lymphocyte apoptosis associated with the acute phase of infection triggers alternatively activated macrophages less able to control parasite replication.198
The question still remains as to how T. cruzi is able to persist, albeit at very low levels, in muscle cells, some neurons, and adipose tissue. Muscle cells produce less NO and more polyamines than phagocytes, which favor parasite multiplication.63 Additionally, myoglobin and neuroglobin are known to scavenge toxic reactive oxygen and nitrogen species,199 while parasite cruzipain and TS induce in cardio- myocytes the production of antiapoptotic molecules. This will protect the host cell from apoptosis induced by oxidative stress, TNF-a, and Fas-FasL pathway and is expected to help the completion of the multiplicative cycle by increasing the life span of the host cell.200,201 Survival of T. cruzi in muscle cells is associated with its ability to limit the expression of NF-KB-dependent genes in these cells, contrary to what happens in epithelial and endothelial cells and fibroblasts.202 It is also proposed that particular metabolic features of muscle and adipose tissue provide a survival advantage for T. cruzi in these cells.24
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