Department of Biological Sciences, University of Idaho, Moscow, ID.
Department of Entomology, Plant Pathology and Nematology, University of Idaho, Moscow, ID; and.
Immunohorizons. 2022 Aug 15;6(8):581-599. doi: 10.4049/immunohorizons.2200055.
Malaria-induced bacteremia has been shown to result from intestinal mast cell (MC) activation. The appearance of MCs in the ileum and increased intestinal permeability to enteric bacteria are preceded by an early Th2-biased host immune response to infection, characterized by the appearance of IL-4, IL-10, mast cell protease (Mcpt)1 and Mcpt4, and increased circulating basophils and eosinophils. Given the functional similarities of basophils and MCs in the context of allergic inflammation and the capacity of basophils to produce large amounts of IL-4, we sought to define the role of basophils in increased intestinal permeability, in MC influx, and in the development of bacteremia in the context of malaria. Upon infection with nonlethal 17XNL, Basoph8 × ROSA-DTα mice or baso (-) mice that lack basophils exhibited increased intestinal permeability and increased ileal MC numbers, without any increase in bacterial 16S ribosomal DNA copy numbers in the blood, relative to baso (+) mice. Analysis of cytokines, chemokines, and MC-associated factors in the ileum revealed significantly increased TNF-α and IL-13 at day 6 postinfection in baso (-) mice compared with baso (+) mice. Moreover, network analysis of significantly correlated host immune factors revealed profound differences between baso (-) and baso (+) mice following infection in both systemic and ileal responses to parasites and translocated bacteria. Finally, basophil depletion was associated with significantly increased gametocytemia and parasite transmission to mosquitoes, suggesting that basophils play a previously undescribed role in controlling gametocytemia and, in turn, mammalian host-to-mosquito parasite transmission.
疟原虫感染引起的菌血症已被证实是由肠道肥大细胞（MC）激活引起的。MC 出现在回肠中，肠道对肠道细菌的通透性增加，这是感染早期 Th2 偏向宿主免疫反应的结果，其特征是出现 IL-4、IL-10、肥大细胞蛋白酶（Mcpt）1 和 Mcpt4，以及循环嗜碱性粒细胞和嗜酸性粒细胞增加。鉴于嗜碱性粒细胞和 MC 在过敏炎症中的功能相似，以及嗜碱性粒细胞产生大量 IL-4 的能力，我们试图确定嗜碱性粒细胞在增加肠道通透性、MC 浸润和疟疾背景下菌血症发展中的作用。在感染非致死性 17XNL 后，Basoph8×ROSA-DTα 小鼠或缺乏嗜碱性粒细胞的 baso（-）小鼠表现出增加的肠道通透性和增加的回肠 MC 数量，而血液中细菌 16S 核糖体 DNA 拷贝数没有增加，与 baso（+）小鼠相比。对回肠中的细胞因子、趋化因子和 MC 相关因子进行分析，结果显示 baso（-）小鼠在感染后第 6 天 TNF-α 和 IL-13 显著增加，与 baso（+）小鼠相比。此外，对显著相关的宿主免疫因子的网络分析表明，在感染后，baso（-）和 baso（+）小鼠在寄生虫和移位细菌的全身和回肠反应中存在明显差异。最后，嗜碱性粒细胞耗竭与配子体血症和寄生虫向蚊子传播的显著增加有关，这表明嗜碱性粒细胞在控制配子体血症方面发挥了以前未描述的作用，进而控制哺乳动物宿主向蚊子传播寄生虫。
