Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses
Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses
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DOI：
10.1128/iai.00597-16
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发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Maekawa, Yoichi
中科院分区：
文献类型：
--
作者：
Asano, Kazunobu;Wu, Zhiliang;Maekawa, Yoichi
传染性微生物经常改变宿主免疫力以逃避免疫消除。旋毛虫是蠕虫家族中一种独特的线虫，其成员寄生在宿主体内的肌肉细胞上，但没有强烈的消除反应。旋毛虫有多种；有些在被包裹的肌肉细胞中发育（例如，旋毛虫），另一些则在不被包裹的细胞中发育（例如，假旋毛虫）。已经确定，旋毛虫感染会影响动物模型中几种实验性免疫疾病的宿主免疫反应；然而，大多数研究都是使用旋毛虫感染进行的。据报道，宿主对螺旋毛虫和伪螺旋毛虫感染的免疫反应是不同的，因此有必要澄清假螺旋毛虫感染如何影响宿主免疫反应。在这项研究中，我们研究了拟螺旋毛虫感染小鼠对宿主体液免疫的影响。我们证明，在用模型抗原免疫的小鼠中，假螺旋毛虫感染减少了抗原特异性 IgG2a 和 IgG2b 抗体 (Ab) 的产生。 γ干扰素 (IFN-γ) 依赖性抗体产生的选择性减少并不是由于 IFN-γ 产生的减少，而是我们发现滤泡辅助 T (Tfh) 细胞分化受损。抗原特异性抗体的亲和力成熟趋于延迟，但在假螺旋毛虫感染的小鼠中并不显着。我们还观察到，假螺旋毛虫感染小鼠的CD11b(+)脾细胞表达CD206和PD-L2，其表型为M2型巨噬细胞，白细胞介素6(IL-6)的产生较弱，可能导致Tfh分化受损。综上所述，我们的结果表明，非包膜旋毛虫感染可选择性抑制体液免疫并抑制 Tfh 分化。
Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-gamma)-dependent Ab production was not due to a decrease in IFN-gamma production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b(+) spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation.