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Background Trypanosoma cruzi is the causative agent for Chagas Disease

Cestari , I. et al. (2010). Inefficient Complement System Clearance of Trypanosoma cruzi Metacyclic Trypomastigotes Enables Resistant Strains to Invade Eukaryotic Cells. P ublic Library Science. 5 : 11. Daniel Ma and Chakrya San. Background

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Background Trypanosoma cruzi is the causative agent for Chagas Disease

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  1. Cestari, I. et al. (2010). Inefficient Complement System Clearance of TrypanosomacruziMetacyclicTrypomastigotes Enables Resistant Strains to Invade Eukaryotic Cells. Public Library Science.5: 11.Daniel Ma and Chakrya San

  2. Background • Trypanosomacruziis the causative agent for Chagas Disease • Complements are part of the secreted effector molecules of the innate immunity that can recognize foreign invaders, leading to formation of membrane attack complex and immune system activation • 3 types of complement activation • Classical pathway via Antibody-Antigen recognition • Lectin pathway via pathogen associated molecular pattern • Alternative pathway via direct C3 recognition • Purpose • 1) Which complement pathways are activated by T. cruzi • 2) The capacity of these strains to resist the complement mediated killing at nearly physiological conditions • 3) Whether the complement system could limit or control T. cruziinvasion of eukaryotic cells. • Experimental Approach • 1) Deposition assays and in vitro assays via ELISA • 2) Kinetic assays • 3) Normal human serum at nearly physiological conditions (50% of serum at 37°C) • 4) Live/dead viability fluorescence Assay

  3. Main Findings • The lectin and alternative pathways are the main activators of the complement system by T. cruzi in non-immune serum • Experimental invasion in vitro in the presence of non-immune human serum at nearly physiological conditions showed that the complement system can limit, but not avoid parasite invasion • Resistance to complement mediated killing is not a strict characteristic of the metacyclictrypomastigote stage of T. cruzi

  4. Critique • It is hard to distinguish between the different strains in figure 2 • Using epimastigote to test complement is not ideal since it only exists in vectors • In the previous slide, the viability fluorescence assay tests a strain that infects primates with human serum • Invasion assay also tests a strains that do not invade primates with Vero cells (African green monkey kidney epithelial cell line) and human serum Take home message • The human complement system can kill metacyclictrypomastigotes of T. cruzi, and the ability to resist the complement system varies between the strains. • T. cruzi strains activate mainly the lectin and alternative pathways of the complement system.

  5. Discussion • The innate immunity molecules (complements) are fairly conserved across species, so it is okay to test different stages of trypanosome against it. • T. cruzi invades cells quickly to escape complement killing. • In figure 3B, the reason why the survival rate goes up at 10 minutes may be because 1) counting error or 2) T cruzi that is resistant to killing has multiplied. • Testing a broad range of strains is required for a good study. • Did not explain future experiments • Strains that are resistant to killing had more invasions. • Invasion does not necessary lead to disease • Lectin is a sugar binding protein that can recognize motifs on the parasite.

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