Endogenous interleukia-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis
Endogenous interleukia-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis
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DOI：
10.1128/iai.69.7.4561-4571.2001
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发表时间：
2001-07-01
影响因子：
3.1
通讯作者：
Schlüter, D
中科院分区：
文献类型：
--
作者：
Deckert, M;Soltek, S;Schlüter, D
为了分析白细胞介素-10（IL-10）在细菌性脑感染中的作用，我们研究了IL-10缺乏的（IL-10（-/-））和野生型（WT）小鼠，后者在原发性和继发性脑白质疏松症中表达高水平的IL-10，IL-10-/-小鼠死于原发性以及继发性白质疏松症，而WT小鼠通过预先腹膜内免疫单核细胞增多性李斯特菌而显著保护免于继发性支原体病。两株均发生脑膜脑炎;然而，在IL-10（-/-）小鼠中，炎症更严重，并与脑水肿增加和多发性脑内出血相关，IL-10（-/-）小鼠招募的白细胞（特别是粒细胞）数量显着增加到大脑和脑内细胞因子（肿瘤坏死因子、IL-1、IL-12、γ干扰素和诱导型一氧化氮合酶）和趋化因子与野生型小鼠相比，巨噬细胞炎性蛋白1 α（crg 2/IP-10、RANTES、MuMig、巨噬细胞炎性蛋白1 α [MIP-1 α]和MIP-1 β）转录增强。尽管有这种明显的炎症反应，脑内L。与WT小鼠相比，IL-10（-/-）小鼠单核细胞生成素特异性CD 8（+）T细胞减少，脑内细菌负荷没有减少。腹膜内感染后，IL-10（-/-）小鼠表现出肝脏过度炎症，但没有更好的细菌清除率;然而，与脑水肿小鼠相反，它们没有死亡，说明靶器官的内在因素对感染的过程和结果有很大影响。
To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10(-/-)) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis, IL-10-/- mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10(-/-) mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages, IL-10(-/-) mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1 alpha [MIP-l alpha], and MIP-1 beta) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8(+) T cells were reduced and the intracerebral bacterial load was not reduced in IL-10(-/-) mice compared to WT mice. Following intraperitoneal infection, IL-10(-/-) mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.