Virulent but not avirulent Mycobacterium tuberculosis can evade the growth inhibitory action of a T helper 1-dependent, nitric oxide Synthase 2-independent defense in mice.
Virulent but not avirulent Mycobacterium tuberculosis can evade the growth inhibitory action of a T helper 1-dependent, nitric oxide Synthase 2-independent defense in mice.
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DOI：
10.1084/jem.20021186
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发表时间：
2002-10-07
期刊：
影响因子：
--
通讯作者：
North RJ
中科院分区：
文献类型：
--
作者：
Jung YJ;LaCourse R;Ryan L;North RJ
小鼠中强毒结核分枝杆菌（Mtb）感染的控制依赖于辅助性T细胞（Th）1介导的免疫的产生，该免疫通过分泌干扰素（IFN）-γ和其他细胞因子来上调巨噬细胞的抗分枝杆菌功能，其中诱导型一氧化氮合酶（NOS）2的合成是必需的事件。作为理解Mtb毒力基础的手段，将不能产生NOS 2（NOS 2-/-）、呼吸爆发NADPH氧化酶复合物的gp 91 Phox亚基（Phox-/-）或任一酶（NOS 2/Phox-/-）的基因缺失小鼠控制Mtb的无毒R1 Rv和H37 Ra菌株的空气传播感染的能力与它们控制毒性H37 Rv菌株感染的能力进行比较。NOS 2 −/−、Phox−/−和NOS 2/Phox−/−小鼠在控制两种无毒力Mtb菌株感染的能力上没有缺陷。相比之下，NOS 2 −/−小鼠，而不是Phox−/−小鼠，无法控制H37 Rv感染，并因嗜肺菌占主导地位的肺部病理而早期死亡。无论是无毒力还是有毒力的结核分枝杆菌感染，其控制都依赖于IFN-γ的合成，并与肺中IFN-γ和NOS 2 mRNA合成的显著增加以及感染部位巨噬细胞产生的NOS 2相关。结果表明，有毒的，但不是无毒的，Mtb可以克服的Th 1依赖性，NOS 2非依赖性防御机制的生长抑制作用。
Control of infection with virulent Mycobacterium tuberculosis (Mtb) in mice is dependent on the generation of T helper (Th)1-mediated immunity that serves, via secretion of interferon (IFN)-γ and other cytokines, to upregulate the antimycobacterial function of macrophages of which the synthesis of inducible nitric oxide synthase (NOS)2 is an essential event. As a means to understanding the basis of Mtb virulence, the ability of gene-deleted mice incapable of making NOS2 (NOS2−/−), gp91Phox subunit of the respiratory burst NADPH-oxidase complex (Phox−/−), or either enzyme (NOS2/Phox−/−), to control airborne infection with the avirulent R1Rv and H37Ra strains of Mtb was compared with their ability control infection with the virulent H37Rv strain. NOS2−/−, Phox−/−, and NOS2/Phox−/− mice showed no deficiency in ability to control infection with either strain of avirulent Mtb. By contrast, NOS2−/− mice, but not Phox−/− mice, were incapable of controlling H37Rv infection and died early from neutrophil-dominated lung pathology. Control of infection with avirulent, as well as virulent Mtb, depended on the synthesis of IFN-γ, and was associated with a substantial increase in the synthesis in the lungs of mRNA for IFN-γ and NOS2, and with production of NOS2 by macrophages at sites of infection. The results indicate that virulent, but not avirulent, Mtb can overcome the growth inhibitory action of a Th1–dependent, NOS2-independent mechanism of defense.
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影响因子：
3.1
作者：
Cooper, AM;Segal, BH;Orme, IM
通讯作者：
Orme, IM
DOI：
10.1016/s0962-8479(97)90004-6
发表时间：
1997-01-01
期刊：
TUBERCLE AND LUNG DISEASE
影响因子：
--
作者：
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Krahenbuhl, JL
影响因子：
3
作者：
Dunn, PL;North, RJ
通讯作者：
North, RJ
DOI：
10.1054/tuld.1999.0214
发表时间：
1999-01-01
期刊：
Tubercle and Lung Disease
影响因子：
--
作者：
Kelley, C. L.;Collins, F. M.
通讯作者：
Collins, F. M.
影响因子：
3.1
作者：
Scanga, CA;Mohan, VP;Chan, J
通讯作者：
Chan, J