ABSENCE OF THE SP/SP RECEPTOR CIRCUITRY IN THE SUBSTANCE P-PRECURSOR KNOCKOUT MICE OR SP RECEPTOR, NEUROKININ (NK)1 KNOCKOUT MICE LEADS TO AN INHIBITED CYTOKINE RESPONSE IN GRANULOMAS ASSOCIATED WITH MURINE TAENIA CRASSICEPS INFECTION
ABSENCE OF THE SP/SP RECEPTOR CIRCUITRY IN THE SUBSTANCE P-PRECURSOR KNOCKOUT MICE OR SP RECEPTOR, NEUROKININ (NK)1 KNOCKOUT MICE LEADS TO AN INHIBITED CYTOKINE RESPONSE IN GRANULOMAS ASSOCIATED WITH MURINE TAENIA CRASSICEPS INFECTION
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DOI：
10.1645/ge-1481.1
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发表时间：
2008-12-01
影响因子：
1.3
通讯作者：
Robinson, Prerna
中科院分区：
文献类型：
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作者：
Garza, Armandina;Weinstock, Joel;Robinson, Prerna
由猪带绦虫引起的脑囊虫病是人类中枢神经系统最常见的寄生虫感染，可导致癫痫发作。小鼠粗头带绦虫囊尾蚴病是猪带绦虫囊尾蚴病的实验模型。与人类感染相似，活寄生虫引起很少或没有肉芽肿性炎症。垂死的寄生虫引发肉芽肿反应。神经肽P物质（SP）刺激T辅助细胞（Th）1细胞因子的产生。在目前的研究中，我们确定是否SP/SP受体电路的SP-前体，preprotachykinin，敲除或SP-受体，神经激肽（NK）1，敲除小鼠的情况下，影响肉芽肿细胞因子的生产。因此，我们通过酶联免疫吸附试验比较了T细胞中Th 1细胞因子白细胞介素（IL）-2和IFN-γ的水平以及Th 2/免疫调节细胞因子IL-4和IL-10的水平。来自感染的C57 BL-6野生型（WT）与SP-前体敲除和NK 1敲除小鼠的巨噬细胞诱导的肉芽肿。我们发现，感染WT衍生的肉芽肿中IL-2、IFN-γ、IL-4和IL-10的平均水平显著高于感染SP前体基因敲除或NK 1受体（NK 1 R）基因敲除小鼠衍生的肉芽肿。Th 2/免疫调节细胞因子IL-4和IL-10的水平在早期肉芽肿（根据寄生虫残留的证据进行组织学分期）中高于两种基因敲除的晚期肉芽肿（无寄生虫残留），而在WT来源的肉芽肿中则相反。本研究确定，SP前体敲除小鼠或NK 1受体敲除小鼠中SP/SP受体回路的缺失导致细胞因子应答受到抑制。
Neurocysticercosis, caused by the cestode Taenia solium, is the most common parasitic infection of the human central nervous system that leads to seizures. Taenia crassiceps cysticercosis in mice is an experimental model for Taenia solium cysticercosis. Similar to the human infection, live parasites cause little or no granulomatous inflammation. Dying parasites initiate a granulomatous reaction. The neuropeptide substance P(SP) stimulated T-helper (Th) 1 cytokine production. In the current study, we determined whether absence of Sp/SP receptor circuitry in the SP-precursor, preprotachykinin, knockout or SP-receptor, neurokinin (NK)1, knockout mice affected granuloma cytokine production. We hence compared the levels of Th1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma and levels of Th2/immuoregulatory cytokines IL-4 and IL-10 by enzyme-linked immunosorbent assay in T. crassiceps-induced granulomas derived from infected C57BL'6 wild-type (WT) versus SP-precursor knockout and NK1 knockout mice. We found that mean levels of IL-2, IFN-gamma, IL-4, and IL-10 in infected WT-derived granulomas were significantly higher than those of granulomas derived from infected SP-precursor knockout or the NK1 receptor (NK1R) knockout mice. Levels of Th2/immunoregulatory cytokines IL-4 and IL-10 were higher in early stage granulomas (histiologically staged on basis of evidence of parasite remnants) versus late stage granulomas (no parasite remnants) of both knockouts, whereas the reverse was noted in WT-derived granulomas. This study established that the absence of an SP/SP receptor circuitry in the SP-precursor knockout mice or NK1 receptor knockout mice led to an inhibited cytokine response.