研究动态
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在环磷酰胺免疫抑制小鼠中,伴随着混合的Th1/Th2免疫类型和M1/M2免疫类型,其对脑炎弓形虫病的易感性增加。

Increased susceptibility to encephalitozoonosis associated with mixed Th1/Th2 profile and M1/M2 profile in mice immunosuppressed with cyclophosphamide.

发表日期:2023 Sep 02
作者: Amanda Miyuki Hidifira, Anuska Marcelino Alvares-Saraiva, Elizabeth Christina Perez, Diva Denelle Spadacci-Morena, Ronalda Silva de Araujo, Maria Anete Lallo
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

骨胼胝体(Encephalitozoon cuniculi)是一种单细胞、产孢、依赖于细胞内的真核生物,属于小孢子虫门。它已知会感染免疫受损和免疫正常的哺乳动物,包括人类。该寄生虫和宿主关系的评估已经使用了体外细胞培养和动物模型。例如,Balb/c和C57BL/6小鼠品系被互相使用,尽管后者由于感染后观察到更高的真菌负荷而被认为更易感染。在本研究中,我们确定了C57BL/6小鼠在接受或不接受免疫抑制剂环磷酰胺(Cy)处理并经腹腔注射接种骨胼胝体后的免疫反应特征。感染14天后,收集血清以分析Th1、Th2和Th17细胞因子水平。此外,进行腹腔冲洗,并收集脾脏样本进行免疫细胞表型分析,收集肝脏、脾脏、肾脏、肺、肠和中枢神经系统(CNS)样本进行组织病理学分析。尽管感染小鼠显示出巨噬细胞的绝对数量减少,但它们显示出M1型表型,CD4+T细胞、CD8+T细胞、B-1和B-2淋巴细胞数量增加,以及Th1炎症细胞因子(干扰素[IFN]-γ、肿瘤坏死因子[TNF]-α和白细胞介素[IL]-2)和Th17为主导。此外,Cy感染的小鼠显示出巨噬细胞数量减少,表现为M1型表型,但CD4+T细胞、CD8+T细胞、B-1和B-2淋巴细胞数量减少,以及Th1炎症细胞因子(IFN-γ、TNF-α和IL-2)和Th2(IL-4)为主导。该组同时显示出更高的真菌负荷,发展出更严重的骨胼胝体病,这与T和B淋巴细胞数量减少以及Th1和Th2细胞因子的混合表型有关。版权所有 © 2023。由Elsevier Inc.出版。
Encephalitozoon cuniculi is a unicellular, spore-forming, obligate intracellular eukaryote belonging to the phylum Microsporidia. It is known to infect mainly immunocompromised and immunocompetent mammals, including humans. The parasite-host relationship has been evaluated using both in vitro cell culturing and animal models. For example, Balb/c and C57BL/6 mouse strains have been used interchangeably, although the latter has been considered more susceptible due to the higher fungal load observed after infection. In the present study, we identified the characteristics of the immune response of C57BL/6 mice treated or not with the immunosuppressant cyclophosphamide (Cy) and challenged with E. cuniculi by intraperitoneal route. After 14 days of infection, serum was collected to analyze Th1, Th2, and Th17 cytokine levels. In addition, peritoneal washes were performed, and the spleen sample was collected for immune cell phenotyping, whereas liver, spleen, kidney, lung, intestine, and central nervous system (CNS) samples were collected for histopathological analysis. Although infected mice displayed a reduced absolute number of macrophages, they showed an M1 profile, an elevated number of CD4+T, CD8+T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-2) and Th17. Furthermore, Cy-Infected mice showed a reduced absolute number of macrophages with an M1 profile but a reduced number of CD4+T, CD8+T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4). This group displayed a higher fungal burden as well and developed more severe encephalitozoonosis, which was associated with a reduced number of T and B lymphocytes and a mixed profile of Th1 and Th2 cytokines.Copyright © 2023. Published by Elsevier Inc.