Inefficient Complement System Clearance of Trypanosoma cruzi Metacyclic Trypomastigotes Enables Resistant Strains to Invade Eukaryotic Cells

Cestari I et al., PloS ONE 5(3):e9721 (2010)

Speaker: Wang Yu-Ren (王昱仁)                                          Time: 14:10-15:00, Oct. 27, 2010

Commentator: Dr. Wang Shu-Ying (王淑鶯 老師)             Place: Room 601

Abstract

Trypanosoma cruzi is a protozoans parasite that causes Chaga’s disease. The Chaga’s disease is a serious health issue from USA to South America. However, the vector triatomine bug, also called kissing bug is a universal insect that transmits the parasites by feeding from human or its feces. So far, the clinical drug treatments are directly against the parasite metabolism, and the effect is not ideal. When metacyclic trypomastigotes enter into human body, it will evade the innate immune system for successful host cell infection and finally lead to death. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. In this study, the authors first used in vitro experiments to find out that lectin and alternative complement pathways activated by vary T. cruzi strains. Then, they used kinetics of invasion assays at nearly physiological conditions to analyze the capacity of these strains to resist the complement-mediated killing. In the invasion assays of Vero cells, the T. cruzi invasion of eukaryotic cell showed limitation by the complement system. Taken together, the complement systems were activated by invadedmetacyclic trypomastigotes, and the degree of activation varied between isolated strains. It is possible that these are other unknown evasion strategies [1, 2]. Therefore, the parasites invaded the host cells and lead to illness. In conclusion, this article provides us the information of the interaction between the extrinsic mechanisms of T. cruzi and the innate immune system. The complement-mediated killing is not a strict characteristic of the metacyclic trypomastigote stage of T. cruzi, and more discoveries of complement receptors and immune evasion strategies may reveal promising targets for therapeutic intervention [3], which could be used to control Chagas disease.

References

1.          Barros VC, et al. The role of salivary and intestinal complement system inhibitors in the midgut protection of triatomines and mosquitoes. PLoS ONE 4(6): e6046 (2009).

2.          Cestari I, et al. Complement C2 receptor inhibitor trispanning confers an increased ability to resist complement-mediated lysis in Trypanosoma cruzi. J Infect Dis 198: 1276–1283 (2008).

3.          Decastro SL. The challenge of Chagas’ disease chemotherapy: an update of drugs assayed against Trypanosoma cruzi. Acta Trop 53: 83–98 (1993).