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 C. elegans. We find apoptotic cell clearance mutant worms are more resistant to pathogenic bacteria of Pseudomonas aeruginosa PA14 and Salmonella typhimurium 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 C. elegans. Taken together, our results provide evidence that insufficient clearance of apoptotic cell can protect Caenorhabditis elegans from bacterial infection through innate immune response activation.

摘要

适当清除细胞凋亡产生的死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，凋亡细胞的去除是由先天免疫系统的极化单核细胞/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，我们目前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的先天免疫反应。我们发现凋亡细胞清除突变蠕虫对铜绿假单胞菌PA14 和鼠伤寒沙门氏菌的病原菌更具抵抗力SL1344 由于先天免疫依赖性病原体反应基因的显着上调。此外，遗传上位性分析表明，在秀丽隐杆线虫中，凋亡细胞清除缺陷可通过 PMK-1 p38 MAPK 和 MPK-1/ERK MAPK 通路激活先天免疫反应。综上所述，我们的结果提供的证据表明，凋亡细胞清除不足可以通过先天免疫反应激活保护秀丽隐杆线虫免受细菌感染。