Constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium
Constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar typhimurium
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DOI：
10.1128/iai.00689-07
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发表时间：
2007-11-01
影响因子：
3.1
通讯作者：
Vazquez-Torres, Andres
中科院分区：
文献类型：
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作者：
McCollister, Bruce D.;Myers, Jesse T.;Vazquez-Torres, Andres
我们已经确定酸性鞘磷脂酶（ASM）是巨噬细胞早期和晚期抗沙门氏菌活性的重要参与者。功能性 ASM 参与巨噬细胞对野生型鼠伤寒沙门氏菌的杀伤活性。 ASM 在早期巨噬细胞杀死沙门氏菌中的作用似乎与活性 NNDPH 吞噬细胞氧化酶酶复合物有关，因为黄素蛋白抑制剂二亚苯基碘鎓不仅阻断了有效的呼吸爆发，而且消除了沙门氏菌在缺乏 ASM 的巨噬细胞中的生存优势。缺乏 ASM 活性还增加了缺乏沙门氏菌致病性岛 2 (SP12) III 型分泌系统易位子和效应子的同基因 Delta spiC::FRT 沙门氏菌菌株的细胞内存活率，表明与 ASM 相关的抗菌活性与细菌的 SP12 状态无关。组成型表达的 ASM 负责这种脂质代谢水解酶在巨噬细胞针对沙门氏菌的先天宿主防御中所发挥的作用。因此，ASM 活性以及神经酰胺、神经节苷脂和中性鞘脂的细胞内浓度和组成在沙门氏菌感染时不会增加。尽管如此，沙门氏菌还是引发了 ASM 分泌部分的显着增加。总的来说，这些发现阐明了组成型 ASM 在小鼠巨噬细胞抗沙门氏菌活性中的新作用。
We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NNDPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM. Lack of ASM activity also increased the intracellular survival of an isogenic Delta spiC::FRT Salmonella strain deficient in a translocator and effector of the Salmonella pathogenicity island 2 (SP12) type III secretion system, suggesting that the antimicrobial activity associated with ASM is manifested regardless of the SP12 status of the bacteria. Constitutively expressed ASM is responsible for the role that this lipid-metabolizing hydrolase plays in the innate host defense of macrophages against Salmonella. Accordingly, the ASM activity and intracellular concentration and composition of ceramide, gangliosides, and neutral sphingolipids did not increase upon Salmonella infection. Salmonella triggered, nonetheless, a significant increase in the secreted fraction of ASM. Collectively, these findings have elucidated a novel role for constitutive ASM in the anti-Salmonella activity of murine macrophages.