Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Global Health Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland.
Parasite Immunol. 2020 Jul;42(7):e12728. doi: 10.1111/pim.12728. Epub 2020 May 25.
Helminth infection represents a major health problem causing approximately 5 million disability-adjusted life years worldwide. Concerns that repeated anti-helminthic treatment may lead to drug resistance render it important that vaccines are developed but will require increased understanding of the immune-mediated cellular and antibody responses to helminth infection. IL-4 or antibody-activated murine macrophages are known to immobilize parasitic nematode larvae, but few studies have addressed whether this is translatable to human macrophages. In the current study, we investigated the capacity of human macrophages to recognize and attack larval stages of Ascaris suum, a natural porcine parasite that is genetically similar to the human helminth Ascaris lumbricoides. Human macrophages were able to adhere to and trap A suum larvae in the presence of either human or pig serum containing Ascaris-specific antibodies and other factors. Gene expression analysis of serum-activated macrophages revealed that CCL24, a potent eosinophil attractant, was the most upregulated gene following culture with A suum larvae in vitro, and human eosinophils displayed even greater ability to adhere to, and trap, A suum larvae. These data suggest that immune serum-activated macrophages can recruit eosinophils to the site of infection, where they act in concert to immobilize tissue-migrating Ascaris larvae.
寄生虫感染是一个主要的健康问题，在全球范围内导致大约 500 万人丧失伤残调整生命年。人们担心反复进行抗寄生虫治疗可能导致耐药性，因此开发疫苗非常重要，但这需要增加对寄生虫感染的免疫介导的细胞和抗体反应的理解。已知白细胞介素 4 或抗体激活的鼠巨噬细胞能够固定寄生线虫幼虫，但很少有研究探讨这种现象是否适用于人类巨噬细胞。在当前的研究中，我们研究了人巨噬细胞识别和攻击猪蛔虫幼虫（一种天然的猪寄生虫，与人类寄生虫蛔虫在基因上相似）的能力。在含有抗蛔虫特异性抗体和其他因子的人或猪血清存在的情况下，人巨噬细胞能够附着并捕获 A 幼虫。对血清激活的巨噬细胞进行的基因表达分析显示，趋化因子 CCL24 是体外培养与 A 幼虫共培养后上调最明显的基因，人嗜酸性粒细胞对 A 幼虫的附着和捕获能力更强。这些数据表明，免疫血清激活的巨噬细胞可以招募嗜酸性粒细胞到感染部位，在那里它们协同作用固定组织迁移的蛔虫幼虫。
