Nonlethal Plasmodium yoelii Infection Drives Complex Patterns of Th2-Type Host Immunity and Mast Cell-Dependent Bacteremia.
Nonlethal Plasmodium yoelii Infection Drives Complex Patterns of Th2-Type Host Immunity and Mast Cell-Dependent Bacteremia.
复制标题
非致命性约氏疟原虫感染导致Th2型宿主免疫和肥大细胞依赖菌血症的复杂模式。
DOI：
10.1128/iai.00427-20
复制
发表时间：
2020-11-16
影响因子：
3.1
通讯作者：
Luckhart S
中科院分区：
文献类型：
--
作者：
Céspedes N;Donnelly E;Garrison S;Haapanen L;Van De Water J;Luckhart S
疟疾强烈倾向于菌血症，这与寄生红细胞的隔离和胃肠道通透性增加有关。对这种破坏的机制知之甚少。在这里，我们评估了与肥大细胞活化和疟疾相关菌血症的啮齿动物模型中的因子的表达。用约氏疟原虫17 XNL感染C57 BL/6 J小鼠，并随时间收集血液和组织以测定细菌16 S DNA、IgE、肥大细胞蛋白酶1（Mcpt-1）和Mcpt-4、Th 1和Th 2细胞因子的循环水平，以及回肠肥大细胞增多症和肠通透性的模式。疟疾强烈倾向于菌血症，这与寄生红细胞的隔离和胃肠道通透性增加有关。对这种破坏的机制知之甚少。在这里，我们评估了与肥大细胞活化和疟疾相关菌血症的啮齿动物模型中的因子的表达。用约氏疟原虫17 XNL感染C57 BL/6 J小鼠，并随时间收集血液和组织以测定细菌16 S DNA、IgE、肥大细胞蛋白酶1（Mcpt-1）和Mcpt-4、Th 1和Th 2细胞因子的循环水平，以及回肠肥大细胞增多症和肠通透性的模式。在约氏疟原虫17 XNL感染后早期检测抗炎细胞因子（白细胞介素-4 [IL-4]、IL-6和IL-10）和MCP-1/CCL 2。随后是IL-9和IL-13的出现，这些细胞因子因其在肥大细胞活化和生长增强活性以及IgE产生中的作用而闻名。随后，在菌血症和肠通透性增加的同时，观察到循环IgE（可诱导肥大细胞脱粒）以及Mcpt-1和Mcpt-4的增加。这些结果表明，约氏疟原虫约氏17 XNL感染诱导产生早期细胞因子，其激活肥大细胞并驱动IgE产生，随后IgE、IL-9和IL-13升高，其维持并增强肥大细胞活化，同时破坏肠道中的蛋白酶/抗蛋白酶平衡，导致上皮损伤和通透性增加。
Malaria strongly predisposes to bacteremia, which is associated with sequestration of parasitized red blood cells and increased gastrointestinal permeability. The mechanisms underlying this disruption are poorly understood. Here, we evaluated the expression of factors associated with mast cell activation and malaria-associated bacteremia in a rodent model. C57BL/6J mice were infected with Plasmodium yoelii yoelli 17XNL, and blood and tissues were collected over time to assay for circulating levels of bacterial 16S DNA, IgE, mast cell protease 1 (Mcpt-1) and Mcpt-4, Th1 and Th2 cytokines, and patterns of ileal mastocytosis and intestinal permeability. Malaria strongly predisposes to bacteremia, which is associated with sequestration of parasitized red blood cells and increased gastrointestinal permeability. The mechanisms underlying this disruption are poorly understood. Here, we evaluated the expression of factors associated with mast cell activation and malaria-associated bacteremia in a rodent model. C57BL/6J mice were infected with Plasmodium yoelii yoelli 17XNL, and blood and tissues were collected over time to assay for circulating levels of bacterial 16S DNA, IgE, mast cell protease 1 (Mcpt-1) and Mcpt-4, Th1 and Th2 cytokines, and patterns of ileal mastocytosis and intestinal permeability. The anti-inflammatory cytokines (interleukin-4 [IL-4], IL-6, and IL-10) and MCP-1/CCL2 were detected early after P. yoelii yoelii 17XNL infection. This was followed by the appearance of IL-9 and IL-13, cytokines known for their roles in mast cell activation and growth-enhancing activity as well as IgE production. Later increases in circulating IgE, which can induce mast cell degranulation, as well as Mcpt-1 and Mcpt-4, were observed concurrently with bacteremia and increased intestinal permeability. These results suggest that P. yoelii yoelii 17XNL infection induces the production of early cytokines that activate mast cells and drive IgE production, followed by elevated IgE, IL-9, and IL-13 that maintain and enhance mast cell activation while disrupting the protease/antiprotease balance in the intestine, contributing to epithelial damage and increased permeability.