Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli.
Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli.
复制标题
接种纳塔利内阿米巴的仓鼠肝脓肿发生过程中炎症反应的特征。
DOI：
10.1371/journal.pntd.0006216
复制
发表时间：
2018-03
影响因子：
3.8
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Guan Y;Feng M;Min X;Zhou H;Fu Y;Tachibana H;Cheng X
纳塔阿米巴是一种具有致病潜力的肠道原虫，可引起阿米巴肝脓肿。它在野生和圈养猕猴中非常普遍。最近，在动物园的非人类灵长类动物饲养员身上检测到包囊，表明纳塔利埃希氏菌可能是一种人畜共患病原体。因此，详细评估纳塔利阿米巴的致病性并与溶组织阿米巴的致病性进行比较非常重要。将 E. nuttalli GY4 和 E. histolytica SAW755 菌株的滋养体接种到仓鼠肝脏中。比较两种寄生虫之间仓鼠促炎因子以及溶组织阿米巴和纳塔利阿米巴毒力因子的表达水平。接种 E. nuttalli 滋养体后 7 天，肝组织中平均坏死面积为 24%，而溶组织 E. histolytica 产生的坏死面积接近 50%。除了纳塔利阿米巴引起的轻度肝组织损伤外，与溶组织阿米巴相比，纳塔利阿米巴局部组织中促炎因子（TNF-α、IL-6和IL-1β）和阿米巴毒力蛋白基因（凝集素、半胱氨酸蛋白酶和阿米巴孔）的表达水平较低。此外，在疾病进展后期，M2型巨噬细胞在E. nuttalli诱导的阿米巴肝脓肿中增加，并且E. nuttalli滋养体的裂解物在体外诱导比溶组织阿米巴更高的精氨酸酶表达。结果表明，阿米巴毒力蛋白在阿米巴感染过程中的差异性分泌引发了各种细胞因子分泌水平的降低，并对巨噬细胞向 M1/M2 平衡的极化产生影响。然而，无论巨噬细胞极化的程度如何，有明确的证据表明，仓鼠的肝脏在感染两种内阿米巴物种后会出现强烈的急性炎症反应。纳塔阿米巴是系统发育上与溶组织内阿米巴最接近的原生动物，在猕猴中非常普遍。先前的研究表明，纳塔利埃希氏菌在仓鼠模型中具有毒性。在本研究中，我们比较了纳塔利阿米巴和溶组织阿米巴仓鼠肝脓肿形成的免疫病理学基础。肝内注射纳塔利阿米巴滋养体后，肝组织出现轻度损伤，在纳塔利阿米巴诱导的肝脓肿边缘检测到宿主促炎因子和阿米巴毒力蛋白基因表达水平较低。此外，在疾病进展的后期，纳塔利大肠杆菌诱导的肝脓肿中替代激活的巨噬细胞增加。在体外，纳塔里阿米巴滋养体的裂解物也比溶组织内阿米巴诱导更高的精氨酸酶表达。巨噬细胞的极化可能会影响动物模型在纳塔里球菌感染期间肝脏急性炎症反应的程度。我们的数据揭示了纳塔利大肠杆菌形成脓肿的新特征。
Entamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica. Trophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro. The results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species. Entamoeba nuttalli is the phylogenetically closest protozoan to Entamoeba histolytica and is highly prevalent in macaques. Previous studies have indicated that E. nuttalli is virulent in a hamster model. In this study, we compared the immunopathological basis of formation of liver abscess in hamsters between E. nuttalli and E. histolytica. Mild liver tissue damage developed after intrahepatic injection of trophozoites of E. nuttalli, and lower expression levels of genes for host proinflammatory factors and amebic virulence proteins were detected at the edges of liver abscesses induced by E. nuttalli. In addition, alternatively activated macrophages were increased in E. nuttalli-induced liver abscesses in the late stage of disease progression. The lysate of E. nuttalli trophozoites also induced higher arginase expression than E. histolytica in vitro. Polarization of macrophages is likely to affect the degree of acute inflammatory reactions in liver in an animal model during E. nuttalli infection. Our data reveal new characteristics of abscess formation by E. nuttalli.