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凋亡细胞清除功能缺陷会激活固有免疫应答,以抵御病原菌。

Defective apoptotic cell clearance activates innate immune response to protect against pathogenic bacteria.

机构信息

Key Laboratory of the Ministry of Education for Medicinal Plant Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in the Northwest of China, College of Life Sciences, Shaanxi Normal University , Xi'an, China.

出版信息

Virulence. 2021 Dec;12(1):75-83. doi: 10.1080/21505594.2020.1857982.

Abstract

Appropriate clearance of dead cells generated by apoptosis is critical to the development of multicellular organisms and tissue homeostasis. In mammals, the removal of apoptotic cell is mediated by polarized monocyte/macrophage populations of the innate immune system. The innate immune system is essential for anti-viral and anti-microbial defense. However, our current understanding of the relationship between apoptotic cell clearance and the innate immune response has remained rather limited. Here, we study how apoptotic cell clearance programs contribute to the innate immune response in . We find apoptotic cell clearance mutant worms are more resistant to pathogenic bacteria of PA14 and SL1344 due to significant upregulation of innate immune-dependent pathogen response genes. In addition, genetic epistasis analysis indicates that defects in apoptotic cell clearance can activate the innate immune response through PMK-1 p38 MAPK and MPK-1/ERK MAPK pathways in . Taken together, our results provide evidence that insufficient clearance of apoptotic cell can protect from bacterial infection through innate immune response activation.

摘要

适当清除凋亡细胞对于多细胞生物的发育和组织稳态至关重要。在哺乳动物中,凋亡细胞的清除是由先天免疫系统中极化的单核细胞/巨噬细胞群介导的。先天免疫系统对于抗病毒和抗微生物防御至关重要。然而,我们对凋亡细胞清除与先天免疫反应之间关系的理解仍然相当有限。在这里,我们研究了凋亡细胞清除程序如何促进秀丽隐杆线虫中的先天免疫反应。我们发现,由于先天免疫依赖性病原体反应基因的显著上调,凋亡细胞清除突变体蠕虫对致病性细菌 PA14 和 SL1344 的抵抗力更强。此外,遗传上位性分析表明,凋亡细胞清除缺陷可以通过秀丽隐杆线虫中的 PMK-1 p38 MAPK 和 MPK-1/ERK MAPK 途径激活先天免疫反应。总之,我们的结果提供了证据,表明凋亡细胞清除不足可以通过先天免疫反应的激活来保护秀丽隐杆线虫免受细菌感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2e2/7781629/914db3211428/KVIR_A_1857982_F0001_OC.jpg

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