Mitsunaga Tetsuya, Norose Kazumi, Aosai Fumie, Horie Hiroshi, Ohnuma Naomi, Yano Akihiko
Department of Infection & Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Department of Infection & Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Parasitol Int. 2019 Feb;68(1):40-47. doi: 10.1016/j.parint.2018.08.010. Epub 2018 Sep 3.
Toxoplasma gondii is a common perorally transmitted parasite; however, its immunopathogenesis in gut-associated tissues remains unclear. Here, we compared disease manifestation in C57BL/6 immunocompetent wild type (WT) mice and immunocompromised interferon (IFN)-γ-deficient (GKO) mice after peroral infection (PI) with T. gondii cysts (Fukaya strain). Strong PI-induced Th1 cytokine expression was detected in WT mice. Moreover, bradyzoite-specific T.g.HSP30/bag1 mRNA was detected in the ileum parenchyma and Peyer's patches (PP), but not in the mesenteric lymph nodes, at 7 days post-infection in WT mice, and was significantly higher than that in GKO mice. Nested PCR showed that parasites existed in ileum parenchyma at days 1 and 1.5 post-PI in GKO and WT mice, respectively. In addition, quantitative competitive-PCR indicated that T. gondii first colonized the PP (day 3 post-PI), followed by the ileum parenchyma and mesenteric lymph nodes, spleen, and portal and aortic blood (day 7 post-PI). Although parasites were consistently more abundant in GKO mice, similar invasion and dissemination patterns were observed in the two hosts. Collectively, these data suggest that some zoites differentiate from tachyzoites to bradyzoites in the ileum and that T. gondii initially invades the ileum parenchyma, and then accumulates and proliferates in the PP before disseminating through the lymphatic systems of both GKO and WT hosts.
刚地弓形虫是一种常见的经口传播寄生虫;然而,其在肠道相关组织中的免疫发病机制仍不清楚。在此,我们比较了C57BL/6免疫健全野生型(WT)小鼠和免疫受损的干扰素(IFN)-γ缺陷(GKO)小鼠经口感染(PI)刚地弓形虫囊肿(深谷株)后的疾病表现。在WT小鼠中检测到强烈的PI诱导的Th1细胞因子表达。此外,在WT小鼠感染后7天,在回肠实质和派尔集合淋巴结(PP)中检测到缓殖子特异性的T.g.HSP30/bag1 mRNA,但在肠系膜淋巴结中未检测到,且显著高于GKO小鼠。巢式PCR显示,在GKO和WT小鼠中,PI后第1天和1.5天,寄生虫分别存在于回肠实质中。此外,定量竞争PCR表明,刚地弓形虫首先定殖于PP(PI后第3天),随后是回肠实质、肠系膜淋巴结、脾脏以及门静脉和主动脉血(PI后第7天)。尽管GKO小鼠体内的寄生虫数量一直更多,但在两种宿主中观察到了相似的侵袭和传播模式。总体而言,这些数据表明,一些速殖子在回肠中分化为缓殖子,并且刚地弓形虫最初侵入回肠实质,然后在PP中聚集和增殖,再通过GKO和WT宿主的淋巴系统传播。