Primary Role of Suppressor of Cytokine Signaling 1 in Mycobacterium bovis BCG Infection.
Primary Role of Suppressor of Cytokine Signaling 1 in Mycobacterium bovis BCG Infection.
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细胞因子信号传导抑制剂 1 在牛分枝杆菌 BCG 感染中的主要作用。
DOI：
10.1128/iai.00376-18
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Yasutomi Y.
中科院分区：
文献类型：
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作者：
Soma S;Kawai S;Inada H; Watanabe K;Mizuno S;Kato S; Matsuo K;Yasutomi Y.
细胞因子信号转导抑制因子1（SOCS 1）是JAK/STAT信号转导的负调控因子，由分枝杆菌感染诱导表达。为了了解SOCS 1在感染过程中的主要功能，我们建立了一种新的系统，在该系统中，重组牛分枝杆菌卡介苗表达显性阴性SOCS 1（rBCG-SOCS 1DN），因为它不会影响未感染细胞中SOCS 1的功能。当C57 BL/6小鼠和RAG 1-/-小鼠经气管内接种rBCG-SOCS 1DN时，肺中的rBCG-SOCS 1DN的量与接种载体对照对应物和野生型BCG的小鼠的肺中的rBCG-SOCS 1DN的量相比显著减少。然而，在NOS 2 −/−小鼠和RAG 1 −/− NOS 2 −/−双敲除小鼠中没有观察到这些显著差异。这些发现表明，SOCS 1抑制一氧化氮（NO）的产生，建立分枝杆菌感染和rBCG-SOCS 1DN有可能成为一个强大的工具，研究SOCS 1在分枝杆菌感染的主要功能。
Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of JAK/STAT signaling and is induced by mycobacterial infection. To understand the major function of SOCS1 during infection, we established a novel system in which recombinant Mycobacterium bovis bacillus Calmette-Guérin expressed dominant-negative SOCS1 (rBCG-SOCS1DN) because it would not affect the function of SOCS1 in uninfected cells. When C57BL/6 mice and RAG1−/−mice were intratracheally inoculated with rBCG-SOCS1DN, the amount of rBCG-SOCS1DN in the lungs was significantly reduced compared to that in the lungs of mice inoculated with a vector control counterpart and wild-type BCG. However, these significant differences were not observed in NOS2−/−mice and RAG1−/−NOS2−/−double-knockout mice. These findings demonstrated that SOCS1 inhibits nitric oxide (NO) production to establish mycobacterial infection and that rBCG-SOCS1DN has the potential to be a powerful tool for studying the primary function of SOCS1 in mycobacterial infection.