The Trypanosoma cruzi Protease Cruzain Mediates Immune Evasion

摘要: Trypanosoma cruzi is the causative agent of Chagas' disease. Novel chemotherapy with drug K11777 targets major cysteine protease cruzain and disrupts amastigote intracellular development. Nevertheless, biological role in infection pathogenesis remains unclear as gene knockout failed due to genetic redundancy. A for T. immune evasion was elucidated a comparative study parental wild type- cruzain-deficient parasites. Wild type did not activate host macrophages during early (<60 min) no increase ∼P iκB detected. The signaling factor NF-κB P65 colocalized on cell surface parasites, proteolytically cleaved. No significant IL-12 expression occurred infected treated LPS BFA, confirming impairment macrophage activation pathways. In contrast, parasites induced activation, detectable phosphorylation, nuclear localization. These were unable develop intracellularly survive within macrophages. IL 12 levels comparable activated controls. Thus hinders stages infection, by interruption mediated pathway. events allow survival replication, may lead spread acute