Negative Regulator Nlrc3-like Maintain the Balanced Innate Immune Response During Mycobacterial Infection in Zebrafish.
Negative Regulator Nlrc3-like Maintain the Balanced Innate Immune Response During Mycobacterial Infection in Zebrafish.
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Nlrc3样负调节因子在斑马鱼分枝杆菌感染期间维持平衡的先天免疫反应
DOI：
10.3389/fimmu.2022.893611
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
The NOD-like receptors (NLRs) have been shown to be involved in infection and autoinflammatory disease. Previously, we identified a zebrafish NLR, nlrc3-like, required for macrophage homeostasis in the brain under physiological conditions. Here, we found that a deficiency of nlrc3-like leads to decreased bacterial burden at a very early stage of Mycobacterium marinum infection, along with increased production of pro-inflammatory cytokines, such as il-1β and tnf-α. Interestingly, myeloid-lineage specific overexpression of nlrc3-like achieved the opposite effects, suggesting that the impact of nlrc3-like on the host anti-mycobacterial response is mainly due to its expression in the innate immune system. Fluorescence-activated cell sorting (FACS) and subsequent gene expression analysis demonstrated that inflammasome activation-related genes were upregulated in the infected macrophages of nlrc3-like deficient embryos. By disrupting asc, encoding apoptosis-associated speck-like protein containing a CARD, a key component for inflammasome activation, the bacterial burden increased in asc and nlrc3-like double deficient embryos compared with nlrc3-like single deficient embryos, implying the involvement of inflammasome activation in infection control. We also found extensive neutrophil infiltration in the nlrc3-like deficient larvae during infection, which was associated with comparable bacterial burden but increased tissue damage and death at a later stage that could be alleviated by administration of dexamethasone. Our findings uncovered an important role of nlrc3-like in the negative regulation of macrophage inflammasome activation and neutrophil infiltration during mycobacterial infection. This highlights the importance of a balanced innate immune response during mycobacterial infection and provides a potential molecular basis to explain how anti-inflammatory drugs can improve treatment outcomes in TB patients whose infection is accompanied by a hyperinflammatory response.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
82.9
作者：
Chen, Chun-Jen;Kono, Hajime;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
NLRC3 负向调节 CD4 T 细胞并影响结核分枝杆菌感染期间的保护性免疫
影响因子：
6.7
作者：
Hu S;Du X;Huang Y;Fu Y;Yang Y;Zhan X;He W;Wen Q;Zhou X;Zhou C;Zhong XP;Yang J;Xiong W;Wang R;Gao Y;Ma L
通讯作者：
Ma L
影响因子：
4.4
作者：
Imamura, Ryu;Wang, Yetao;Suda, Takashi
通讯作者：
Suda, Takashi
影响因子：
56.9
作者：
Darwin, KH;Ehrt, S;Nathan, CF
通讯作者：
Nathan, CF