Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, IIB-INTECH, National Research Council of Argentina (CONICET), Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
J Biol Chem. 2013 Jul 12;288(28):20208-16. doi: 10.1074/jbc.M113.453282. Epub 2013 May 29.
Brucella spp. and Trypanosoma cruzi are two intracellular pathogens that have no evolutionary common origins but share a similar lifestyle as they establish chronic infections for which they have to circumvent the host immune response. Both pathogens have a virulence factor (prpA in Brucella and tcPrac in T. cruzi) that induces B-cell proliferation and promotes the establishment of the chronic phase of the infectious process. We show here that, even though PrpA promotes B-cell proliferation, it targets macrophages in vitro and is translocated to the cytoplasm during the intracellular replication phase. We observed that PrpA-treated macrophages induce the secretion of a soluble factor responsible for B-cell proliferation and identified nonmuscular myosin IIA (NMM-IIA) as a receptor required for binding and function of this virulence factor. Finally, we show that the Trypanosoma cruzi homologue of PrpA also targets macrophages to induce B-cell proliferation through the same receptor, indicating that this virulence strategy is conserved between a bacterial and a protozoan pathogen.
布鲁氏菌属和克氏锥虫是两种胞内病原体，它们没有进化上的共同起源，但具有相似的生活方式，因为它们建立了慢性感染，必须规避宿主的免疫反应。这两种病原体都有一种毒力因子（布鲁氏菌中的 prpA 和克氏锥虫中的 tcPrac），它能诱导 B 细胞增殖，并促进感染过程的慢性阶段的建立。我们在这里表明，尽管 PrpA 能促进 B 细胞增殖，但它在体外靶向巨噬细胞，并在细胞内复制阶段被转运到细胞质中。我们观察到，用 PrpA 处理的巨噬细胞会诱导分泌一种能促进 B 细胞增殖的可溶性因子，并鉴定出非肌肉肌球蛋白 IIA（NMM-IIA）作为结合和发挥这种毒力因子功能所必需的受体。最后，我们表明，PrpA 的克氏锥虫同源物也通过相同的受体靶向巨噬细胞，诱导 B 细胞增殖，这表明这种毒力策略在细菌和原生动物病原体之间是保守的。
