The crosstalk between microbial sensors ELMO1 and NOD2 shape intestinal immune responses.
The crosstalk between microbial sensors ELMO1 and NOD2 shape intestinal immune responses.
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DOI：
10.1080/21505594.2023.2171690
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发表时间：
2023-12
期刊：
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
微生物传感器在维持细胞内稳态中起着重要作用。我们的知识是有限的微生物传感如何帮助在不同的免疫反应及其与炎症性疾病的联系。最近，我们已经证实，ELMO 1（吞噬和细胞运动蛋白-1）存在于胞质中参与病原体的感应，吞噬，和肠道炎症。在这里，我们发现ELMO 1与另一种传感器NOD 2（含核苷酸结合寡聚化结构域蛋白2）相互作用，该传感器识别细菌细胞壁组分胞壁酰二肽（MDP）。NOD 2的多态性与克罗恩病（CD）的发病机制有关。有趣的是，我们发现ELMO 1和突变型NOD 2（L1007 fs）的过表达不能清除CD相关的粘附侵袭性E。coli（AIEC-LF82）。上皮细胞中ELMO 1-NOD 2相互作用的功能意义通过使用来自ELMO 1和NOD 2 KO小鼠的肠源性单层（EDM）来评估。随后，我们还评估了耗尽ELMO 1或NOD 2或两者的J774巨噬细胞中的免疫应答。用AIEC-LF 82感染鼠EDM在ELMO 1-KO、NOD 2 KO EDM和用NOD 2抑制剂处理的ELMO 1 KO EDM中显示出更高的细菌负荷。小鼠巨噬细胞显示ELMO 1和NOD 2的下调与受损的细菌清除相关，这与减少促炎细胞因子和活性氧有关。我们的研究结果表明，肠道感染和炎症性疾病中微生物传感器之间的串扰影响细菌负荷和疾病发病机制的命运。
Microbial sensors play an essential role in maintaining cellular homoeostasis. Our knowledge is limited on how microbial sensing helps in differential immune response and its link to inflammatory diseases. Recently we have confirmed that ELMO1 (Engulfment and Cell Motility Protein-1) present in cytosol is involved in pathogen sensing, engulfment, and intestinal inflammation. Here, we show that ELMO1 interacts with another sensor, NOD2 (Nucleotide-binding oligomerization domain-containing protein 2), that recognizes bacterial cell wall component muramyl dipeptide (MDP). The polymorphism of NOD2 is linked to Crohn’s disease (CD) pathogenesis. Interestingly, we found that overexpression of ELMO1 and mutant NOD2 (L1007fs) were not able to clear the CD-associated adherent invasive E. coli (AIEC-LF82). The functional implications of ELMO1-NOD2 interaction in epithelial cells were evaluated by using enteroid-derived monolayers (EDMs) from ELMO1 and NOD2 KO mice. Subsequently we also assessed the immune response in J774 macrophages depleted of either ELMO1 or NOD2 or both. The infection of murine EDMs with AIEC-LF82 showed higher bacterial load in ELMO1-KO, NOD2 KO EDMs, and ELMO1 KO EDMs treated with NOD2 inhibitors. The murine macrophage cells showed that the downregulation of ELMO1 and NOD2 is associated with impaired bacterial clearance that is linked to reduce pro-inflammatory cytokines and reactive oxygen species. Our results indicated that the crosstalk between microbial sensors in enteric infection and inflammatory diseases impacts the fate of the bacterial load and disease pathogenesis.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.3390/antiox10020313
发表时间：
2021-02-19
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Herb M;Schramm M
通讯作者：
Schramm M