MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.
MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.
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DOI：
10.4049/jimmunol.1401056
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Maizels RM
中科院分区：
文献类型：
--
作者：
Reynolds LA;Harcus Y;Smith KA;Webb LM;Hewitson JP;Ross EA;Brown S;Uematsu S;Akira S;Gray D;Gray M;MacDonald AS;Cunningham AF;Maizels RM
蠕虫寄生虫仍然是世界范围内最常见的感染原因之一，但控制它们排出的免疫信号通路仍然知之甚少。C57BL/6小鼠长期易感染胃肠道蠕虫寄生虫多回。在这篇文章中，我们报道了C57BL/6小鼠缺乏介导TLRs和IL-1家族成员信号转导的适配蛋白MyD88的小鼠对多脑回H。伴随着寄生虫排泄的增加，MyD88基因缺陷的小鼠表现出从肠系膜淋巴结CD4+细胞产生IL-4和IL-17A的增加。此外，MyD88−/−小鼠在感染部位周围形成了大量的肠道肉芽肿，这在MyD88充足的C57BL/6小鼠中没有看到，当通过适配器蛋白TRIF(含有TIR结构域的适配器诱导的干扰素-β适配器蛋白)的信号也被去除时，也没有看到这种情况。单独缺乏TLR2、TLR4、TLR5或TLR9的小鼠没有表现出增强的寄生虫排出能力，这表明这些TLRs信号冗余，以维持野生型小鼠对多脑回的易感性。为了进一步研究依赖于MyD88的信号通路，我们用多回小鼠感染了IL-1R1−/−小鼠。与野生型小鼠相比，这种基因型鼠的肉芽肿数量增加，但没有增加寄生虫的排泄。因此，IL-1R-MyD88途径与抑制肉芽肿的形成有关；然而，MyD88缺陷小鼠的保护性免疫似乎是独立于肉芽肿的。与IL-1R1−/−和MyD88−/−小鼠一样，缺乏通过1型干扰素受体(即IFNAR1−/−)传递信号的动物也会患上肠道肉芽肿。因此，IL-1R1、MyD88和1型干扰素受体信号可能提供了阻止体内肉芽肿形成的途径，但额外的MyD88介导的信号与易感C57BL/6小鼠的保护性免疫抑制有关。
Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4+ cells. In addition, MyD88−/− mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain–containing adapter–inducing IFN-β adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1−/− mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R–MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1−/− and MyD88−/− mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1−/−) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice.
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影响因子：
1.5
作者：
Hewitson, James P.;Grainger, John R.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.
DOI：
10.1084/jem.20101074
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Grainger JR;Smith KA;Hewitson JP;McSorley HJ;Harcus Y;Filbey KJ;Finney CA;Greenwood EJ;Knox DP;Wilson MS;Belkaid Y;Rudensky AY;Maizels RM
通讯作者：
Maizels RM
影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
DOI：
10.1084/jem.194.3.355
发表时间：
2001-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Helmby H;Takeda K;Akira S;Grencis RK
通讯作者：
Grencis RK
影响因子：
6.7
作者：
Hewitson, James P.;Ivens, Al C.;Maizels, Rick M.
通讯作者：
Maizels, Rick M.