Phagocytosis and phagosome acidification are required for pathogen processing and MyD88-dependent responses to Staphylococcus aureus.
Phagocytosis and phagosome acidification are required for pathogen processing and MyD88-dependent responses to Staphylococcus aureus.
复制标题
DOI：
10.4049/jimmunol.1000110
复制
发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Stuart LM
中科院分区：
文献类型：
--
作者：
Ip WK;Sokolovska A;Charriere GM;Boyer L;Dejardin S;Cappillino MP;Yantosca LM;Takahashi K;Moore KJ;Lacy-Hulbert A;Stuart LM
先天免疫对于保护机体免受微生物侵害至关重要，它由体液效应物（如细胞因子）和细胞免疫防御（包括吞噬细胞（如巨噬细胞））共同介导。在被吞噬细胞内化后，微生物被运送到吞噬小体中，吞噬小体是一种复杂的细胞内细胞器，在杀死微生物方面发挥着重要作用。然而，这种细胞器在细胞因子反应和微生物感知中的作用尚不明确。在这里，我们评估了吞噬体在先天免疫感知中的作用，并证明了在对革兰氏阳性细菌金黄色葡萄球菌的反应中，吞噬作用和模式识别受体信号的关键相互依赖性。我们发现，吞噬作用对于启动对金黄色葡萄球菌的最佳myd88依赖性反应是必不可少的。在tlr依赖性细胞因子产生之前，细菌不仅必须被吞噬，而且还必须被输送到酸性吞噬体中。在这里，酸激活的宿主酶消化内化的细菌，以释放其他隐细菌衍生的配体，这些配体启动液泡的反应。重要的是，在吞噬体酸化受到干扰的巨噬细胞中，对金黄色葡萄球菌的受损反应可以通过添加溶葡萄球菌蛋白来恢复，溶葡萄球菌蛋白是一种细菌内肽酶，在中性pH下具有活性，可以替代酸激活的宿主酶。总之，这些观察结果描述了吞噬与模式识别受体信号传导的相互依赖性，并表明增强液泡功能和信号传导的治疗方法可能是增加宿主对金黄色葡萄球菌反应的有用策略。
Innate immunity is vital for protection from microbes and is mediated by both humoral effectors, such as cytokines, and cellular immune defenses, including phagocytic cells such as macrophages. After internalization by phagocytes, microbes are delivered into a phagosome, a complex intracellular organelle with a well-established and important role in microbial killing. However, the role of this organelle in cytokine responses and microbial sensing is less well defined. Here we assess the role of the phagosome in innate immune sensing and demonstrate the critical interdependence of phagocytosis and pattern recognition receptor signaling during response to the Gram-positive bacteria Staphylococcus aureus. We show that phagocytosis is essential to initiate optimal MyD88-dependent response to Staphylococcus aureus. Prior to TLR-dependent cytokine production bacteria must not only be engulfed but also delivered into acidic phagosomes. Here acid-activated host enzymes digest the internalized bacteria to liberate otherwise cryptic bacterial-derived ligands that initiate responses from the vacuole. Importantly, in macrophages in which phagosome acidification is perturbed, the impaired response to Staphylococcus aureus can be rescued by addition of lysostaphin, a bacterial endopeptidase active at neutral pH that can substitute for the acid-activated host enzymes. Together these observations delineate the inter-dependence of phagocytosis with pattern recognition receptor signaling and suggest that therapeutics to augment functions and signaling from the vacuole may be useful strategies to increase host responses to Staphylococcus aureus.
登录
查看更多内容
影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1083/jcb.124.5.677
发表时间：
1994-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Desjardins M;Huber LA;Parton RG;Griffiths G
通讯作者：
Griffiths G
甘露糖结合凝集素增强了吞噬体的Toll样受体2和6信号传导。
影响因子：
15.3
作者：
Ip, W. K. Eddie;Takahashi, Kazue;Moore, Kathryn J.;Stuart, Lynda M.;Ezekowitz, R. Alan B.
通讯作者：
Ezekowitz, R. Alan B.
影响因子：
3.6
作者：
Bera, A;Herbert, S;Götz, F
通讯作者：
Götz, F
DOI：
10.1179/096805104225006525
发表时间：
2004-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Latz, E;Visintin, A;Golenbock, DT
通讯作者：
Golenbock, DT