Carasi Paula, Rodríguez Ernesto, da Costa Valeria, Frigerio Sofía, Brossard Natalie, Noya Verónica, Robello Carlos, Anegón Ignacio, Freire Teresa
Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Facultad de Medicina, Departamento de Inmunobiología, Universidad de República, Montevideo, Uruguay.
Departamento de Bioquimica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Front Immunol. 2017 Jul 26;8:883. doi: 10.3389/fimmu.2017.00883. eCollection 2017.
, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC) maturation and alternative activation of macrophages. In this paper, we show that infection in mice induces the upregulation of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during infection. Finally, HO-1 expression during infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by in the host and provide alternative checkpoints to control fasciolosis.
（文本中未提及具体名称，推测为肝片吸虫），也被称为肝吸虫，是一种吸虫，可感染家畜和人类，导致肝片吸虫病，由于其在全球范围内的分布以及造成的巨大经济损失，这种人畜共患病的重要性日益增加。这种寄生虫通过免疫调节树突状细胞（DC）成熟和巨噬细胞的替代激活，诱导强烈的Th2和调节性T免疫反应，从而对宿主免疫系统进行免疫调节。在本文中，我们表明小鼠感染（肝片吸虫）会诱导血红素加氧酶-1（HO-1）的上调，HO-1是游离血红素分解代谢中的限速酶，可调节宿主炎症反应。我们展示并鉴定了感染动物腹膜中感染期间表达HO-1的两种不同抗原呈递细胞群体。表达高水平HO-1的细胞表达中等水平的F4/80，但CD11c、CD38、TGFβ和IL-10表达较高，表明它们对应于调节性DC。另一方面，表达中等水平HO-1的细胞表达高水平的F4/80、CD68、Ly6C和FIZZ-1，表明它们可能对应于替代激活的巨噬细胞。此外，用合成金属卟啉CoPP进行HO-1的药理学诱导促进了（肝片吸虫）感染，增加了与该疾病相关的临床症状。相反，用HO-1抑制剂SnPP治疗可保护小鼠免受寄生虫感染，表明HO-1在（肝片吸虫）感染期间起重要作用。最后，（肝片吸虫）感染期间HO-1的表达与肝脏和腹膜中的TGFβ和IL-10水平相关，表明HO-1在感染期间控制这些免疫调节细胞因子的表达，有利于寄生虫在宿主体内存活。这些结果有助于阐明（肝片吸虫）在宿主中诱导的免疫调节机制，并为控制肝片吸虫病提供了替代检查点。
