A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection
A defective Th1 response of the spleen in the initial phase may explain why splenectomy helps prevent a Listeria infection
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DOI：
10.1111/j.1365-2249.2005.02735.x
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发表时间：
2005-04-01
影响因子：
4.6
通讯作者：
Seki, S
中科院分区：
文献类型：
--
作者：
Kuranaga, N;Kinoshita, M;Seki, S
单核细胞增生性李斯特菌(李斯特菌)已知在肝脏中生长和增殖，而脾切除术诱导宿主抵抗李斯特菌感染，尽管脾切除术抑制Th1反应。因此，脾切除帮助防止李斯特菌生长的机制仍有待阐明。在静脉注射之后。Listeria(1×10(6)CFU)的攻击在C57BL/6小鼠体内，直到48h，李斯特菌在脾中迅速增加，而在肝脏中不再增加，但在这一初始阶段后，李斯特菌在肝脏中显著增长。相反，预先切除脾的小鼠，尽管攻毒后24小时血清中的干扰素-γ和IL-12水平显著低于假手术组，但攻毒后小鼠肝脏中的李斯特菌未见明显生长。感染后6h的小鼠肝白细胞产生大量的干扰素-γ，而脾单个核细胞则不产生，而攻毒后24 h的脾白细胞产生大量的干扰素。直到感染后6h，脾组织匀浆中的干扰素-γ和IL-12水平均显著低于肝组织匀浆。在李斯特菌感染的早期阶段，这种缺陷的脾Th1反应被IL-18腹腔注射纠正。就在李斯特菌挑战之后注射。我们的发现表明，李斯特菌在最初阶段利用了脾中缺陷的Th1环境，然后克服了肝脏的宿主防御机制。
Listeria monocytogenes (Listeria) are known to grow and proliferate in the liver while a splenectomy induces host resistance against a Listeria infection despite the fact that a splenectomy inhibits the Th1 response. Therefore, the mechanism by which a splenectomy helps to prevent the growth of Listeria still remains to be elucidated. After an i.v. challenge of Listeria (1 x 10(6) CFU) in C57BL/6 mice, Listeria rapidly increased in the spleen but not in the liver until 48 h. However, after this initial phase, Listeria remarkably grew in the liver. In contrast, when the mice received a splenectomy beforehand, no remarkable growth of Listeria in the liver was observed after Listeria challenge despite the fact that serum IFN-gamma and IL-12 levels at 24 h after Listeria challenge were significantly lower than those in the sham mice. However, the liver leucocytes from mice by 6 h after infection produced a substantial amount of IFN-gamma while spleen MNC did not, whereas spleen leucocytes at 24 h after Listeria challenge did. Consistently, the IFN-gamma and IL-12 levels in the tissue homogenates of the spleen were significantly lower than in those of the liver until 6 h after infection. This defective spleen Th1 response in the early phase of Listeria infection was corrected by an IL-18 i.p. injection just after the Listeria challenge. Our findings suggest that Listeria exploit the defective Th1 environment of the spleen in the initial phase and afterwards overcome the host defense mechanism of the liver.