Trypanosoma cruziexposes phosphatidylserine as an evasion mechanism

Abstract

Chagas disease is caused by Trypanosoma cruzi and affects 18 million people in Central and South America. Here we analyzed the exposure of phosphatidylserine by the different forms of the parasite life cycle. Only the infective trypomastigotes, but not the epimastigotes or intracellular amastigotes, expose this phospholipid. This triggers a transforming growth factor beta signaling pathway, based on phosphorylated Smad 2 nuclear translocation, leading to iNOS disappearance in infected macrophages. This macrophage deactivation favors the survival of this intracellular parasite. Thus, phosphatidylserine exposure may be used by T. cruzi to evade innate immunity and be a common feature of obligate intracellular parasites that have to deal with activated macrophages.

Intraphagosomal Peroxynitrite as a Macrophage-derived Cytotoxin against Internalized Trypanosoma cruzi

“…For instance, Leishmania donovani promastigotes are internalized by macrophages without eliciting a respiratory burst, thereby avoiding O 2 . production (85), and can also down-regulate macrophage ⅐ NO production (86). Additionally, T. cruzi as well as other pathogenic trypanosomatids have an ample and well distributed set of antioxidant enzymes to cope with reactive oxygen and nitrogen species (28,52,87,88).…”

Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease

“…Apoptosis of leukocytes, cardiomyocytes and parasites is a common feature of cardiac inflammatory infiltrates in dogs acutely infected with T. cruzi (53). Similar to apoptotic cells, trypomastigote forms of T. cruzi express phosphatidylserine on the surface, and engage TGF-β signaling pathways in macrophages (54). However, the macrophage receptor involved remains unidentified.…”

“…However, the macrophage receptor involved remains unidentified. This study suggests that apoptotic mimicry through exposure of phosphatidylserine deactivates macrophages and helps parasite replication (54). Furthermore, infection with T. cruzi triggers apoptosis of T and B lymphocytes, and lymphocyte apoptosis has immunoregulatory implications for host immune responses (55).…”

Annexins in Translational Research: HIDDEN Treasures to Be Found

“…It acts as a first line of defense against pathogen attack, and, not surprisingly, pathogens have evolved sophisticated strategies to overcome these cellular defense mechanisms or even use them to their advantage. Trypanosoma cruzi, for example, presents PS on the cell surface of trypomastigote stage in order to mimic the anti-inflammatory effects of apoptotic cells, thus evading the host innate immune response [111]. A similar mechanism of apoptotic mimicry to balance inflammation is also used by Toxoplasma gondii [112] and Leishmania braziliensis [113], although it remains to be studied whether the immunomodulatory function also depends on the recruitment of AnxA1.…”