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Abstract：
Chagas disease is caused by the intracellular protozoan parasite Trypanosoma cruzi. This disease affects mainly rural areas in Central and South America, where the insect vector is endemic. However, this disease has become a world health problem since migration has spread it to other continents. It is a complex disease with many reservoirs and vectors and high genetic variability. One of the host proteins involved in the pathogenesis is SLAMF1. This immune receptor acts during the infection of macrophages controlling parasite replication and thus affecting survival in mice but in a parasite strain-dependent manner. Therefore, we studied the role of SLAMF1 by quantitative proteomics in a macrophage in vitro infection and the different responses between Y and VFRA strains of Trypanosoma cruzi. We detected different significant up- or downregulated proteins involved in immune regulation processes, which are SLAMF1 and/or strain-dependent. Furthermore, independently of SLAMF1, this parasite induces different responses in macrophages to counteract the infection and kill the parasite, such as type I and II IFN responses, NLRP3 inflammasome activation, IL-18 production, TLR7 and TLR9 activation specifically with the Y strain, and IL-11 signaling specifically with the VFRA strain. These results have opened new research fields to elucidate the concrete role of SLAMF1 and discover new potential therapeutic approaches for Chagas disease.
摘要：
锥虫病是由细胞内原生动物寄生虫克氏锥虫引起的。这种疾病主要影响中美洲和南美洲的农村地区，昆虫媒介是地方性的。然而,自从移民将其传播到其他大陆以来，这种疾病已成为世界健康问题。它是一种复杂的疾病，具有许多水库和媒介以及高度的遗传变异性。与发病机理有关的宿主蛋白之一是SLAMF1。这种免疫受体在巨噬细胞感染期间起作用，控制寄生虫的复制，从而影响小鼠的存活，但以寄生虫菌株依赖的方式起作用。因此,我们通过定量蛋白质组学研究了SLAMF1在巨噬细胞体外感染中的作用以及克氏锥虫Y和VFRA菌株之间的不同反应。我们检测到不同的显著上调或下调的蛋白质参与免疫调节过程，它们是SLAMF1和/或应变依赖性的。此外，独立于SLAMF1，这种寄生虫在巨噬细胞中诱导不同的反应以抵抗感染并杀死寄生虫，如I型和II型IFN反应，NLRP3炎性体激活，IL-18生产，TLR7和TLR9特异性地与Y菌株活化，和IL-11特异性地与VFRA菌株进行信号传导。这些结果开辟了新的研究领域，阐明了SLAMF1的具体作用，并发现了查加斯病的新的潜在治疗方法。
