坏死性下垂
先天免疫系统
炎症体
NLRC4型
裂谷1
细胞生物学
程序性细胞死亡
生物
信号转导
目标2
半胱氨酸蛋白酶
免疫系统
时尚
NALP3
细胞凋亡
炎症
免疫学
半胱氨酸蛋白酶1
生物化学
作者
Balamurugan Sundaram,Rajendra Karki,Thirumala‐Devi Kanneganti
出处
期刊:ImmunoHorizons
[The American Association of Immunologists]
日期:2022-03-01
卷期号:6 (3): 243-252
被引量:4
标识
DOI:10.4049/immunohorizons.2100118
摘要
Hosts rely on the innate immune system to clear pathogens in response to infection. Pathogen-associated molecular patterns bind to innate immune receptors and engage activation of downstream signaling to initiate a host immune response to fight infection. A key component of this innate response is programmed cell death. Recent work has highlighted significant cross-talk and functional redundancy between cell death pathways, leading to the discovery of PANoptosis, an inflammatory programmed cell death pathway dependent on PANoptosomes, which are innate immune danger-sensing complexes that activate inflammatory cell death and contain caspases with or without inflammasome components and receptor interacting protein homotypic interaction motif-containing proteins. Although PANoptosis has been characterized in response to a growing number of pathogens, inflammatory diseases, and cancer, its role and the functional consequences of PANoptotic component modulation during NLR family CARD domain-containing protein 4 (NLRC4) activation by Pseudomonas aeruginosa infection remain unknown. In this study, we show that P. aeruginosa can induce PANoptosis in mouse bone marrow-derived macrophages (BMDMs). Only the combined deletion of caspase-1, -11, -8, and RIPK3 protected mouse BMDMs from cell death. Moreover, we showed that PANoptotic components act in a compensatory manner; in the absence of NAIP5 and NLRC4 during P. aeruginosa challenge, activation of caspase-1, -3, -7, and -8 was reduced, whereas alternative cell death molecules such as RIPK1 and MLKL were activated in mouse BMDMs. Taken together, these data highlight the extensive cross-talk between cell death signaling molecules and showcase the plasticity of the system.
科研通智能强力驱动
Strongly Powered by AbleSci AI