Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice.
Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice.
复制标题
肝巨噬细胞在小鼠多房棘球绦虫建立中的双重作用
DOI：
10.3389/fimmu.2020.600635
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Wen H
中科院分区：
文献类型：
--
作者：
Wang H;Zhang CS;Fang BB;Hou J;Li WD;Li ZD;Li L;Bi XJ;Li L;Abulizi A;Shao YM;Lin RY;Wen H
多房棘球绦虫幼虫主要位于肝脏中，引起肿瘤样寄生虫病，泡状棘球蚴病（AE），其特征在于病变周围各种免疫细胞（包括巨噬细胞）的浸润增加，产生“免疫抑制”微环境，有利于其持续感染。然而，肝巨噬细胞在宿主防御E.多房性感染的定义仍然不明确。采用人肝组织和小鼠实验性E.在多房巨噬细胞的感染过程中，我们研究了肝巨噬细胞的表型和功能。在本研究中，我们发现大量的CD 68+巨噬细胞聚集在人类AE样品的肝脏中的后囊蚴病变周围，并且S100 A9+促炎性细胞和巨噬细胞都可以被激活。（M1表型）和CD 163+抗炎（M2表型）巨噬细胞在近端肝组织（CLT）中显著高于远端肝组织（DLT），而M2巨噬细胞代表主要的巨噬细胞群体。此外，还发现E.感染多房巨噬细胞的小鼠肝脏中巨噬细胞（F4/80+）浸润早在第5天就大量增加，并且浸润的巨噬细胞主要是单核细胞来源的巨噬细胞（CD 11bhi F4/80 int MoMFs），其在E.在感染的慢性阶段，多房性巨噬细胞感染，然后极化为M2表型的抗炎巨噬细胞（CD 206+）。我们进一步表明，在E.多房性感染损害了蠕虫的排出，并伴随着肝纤维化的减少，产生了高寄生虫负荷。这些结果提示，肝巨噬细胞在大肠杆菌的建立和发育过程中可能起着双重作用。其中M1巨噬细胞促进早期幼虫清除，而M2巨噬细胞有利于持续性后绦虫感染。
Echinococcus multilocularis larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an “immunosuppressive” microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against E. multilocularis infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of E. multilocularis, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68+ macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9+ proinflammatory (M1 phenotype) and CD163+ anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore, E. multilocularis-infected mice exhibited a massive increase in macrophage (F4/80+) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11bhi F4/80int MoMFs) that preferentially differentiated into the M1 phenotype (iNOS+) at the early stage of E. multilocularis infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206+) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before E. multilocularis infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of E. multilocularis metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.
登录
查看更多内容
影响因子：
9.2
作者：
Garrido VV;Dulgerian LR;Stempin CC;Cerbán FM
通讯作者：
Cerbán FM
影响因子：
25.7
作者：
Aji, Tuerganaili;Dong, Jia-Hong;Wen, Hao
通讯作者：
Wen, Hao
影响因子：
3.9
作者：
Andrade, MA;Siles-Lucas, M;Muro, A
通讯作者：
Muro, A
影响因子：
2.2
作者：
Bellanger, Anne-Pauline;Pallandre, Jean-Rene;Millon, Laurence
通讯作者：
Millon, Laurence
影响因子：
2.2
作者：
KANAZAWA, T;ASAHI, H;STADECKER, MJ
通讯作者：
STADECKER, MJ