Two Distinct Mechanisms For Induction of Dendritic Cell Apoptosis in Response to Intact Streptococcus pneumoniae 1
Two Distinct Mechanisms For Induction of Dendritic Cell Apoptosis in Response to Intact Streptococcus pneumoniae 1
复制标题
完整肺炎链球菌诱导树突状细胞凋亡的两种不同机制 1
作者：
J. Colino;C. Snapper
凋亡树突状细胞（DC）在诱导免疫方面是无效的。因此，在原发性感染期间调节DC活力的参数将有助于确定后续免疫反应的结果。在这方面，病原体已经开发出促进DC凋亡以平衡新生的初级免疫应答的策略。我们证明，使用培养的骨髓来源的DC，肺炎链球菌可以通过两种不同的机制诱导DC凋亡：1）快速，半胱天冬酶非依赖性的凋亡诱导机制，严重依赖于肺炎链球菌溶血素的细菌表达，和2）延迟发病，半胱天冬酶依赖性的凋亡诱导机制与终末DC成熟。延迟发生的细胞凋亡不需要细菌内化，而是由细菌被膜下成分和骨髓来源的DC（可能是Toll样）受体的相互作用触发，所述DC以髓样分化因子88依赖性方式起作用。在这方面，重多糖包封干扰DC成熟和凋亡诱导。相反，CD 95/CD 95配体相互作用和TNF-α似乎在细胞凋亡延迟发生中均不起作用。这些数据是第一个定义两个机制不同的途径，DC细胞凋亡诱导响应细胞外细菌，可能有重要的后果，建立抗菌免疫。
Apoptotic dendritic cells (DCs) are ineffective at inducing immunity. Thus, parameters that regulate DC viability during a primary infection will help to determine the outcome of the subsequent immune response. In this regard, pathogens have developed strategies to promote DC apoptosis to counterbalance the nascent primary immune response. We demonstrate, using cultured bone marrow-derived DCs, that Streptococcus pneumoniae can induce DC apoptosis through two distinct mechanisms: 1) a rapid, caspase-independent mechanism of apoptosis induction, critically dependent on bacterial expression of pneumolysin, and 2) a delayed-onset, caspase-dependent mechanism of apoptosis induction associated with terminal DC maturation. Delayed-onset apoptosis does not require bacterial internalization, but rather is triggered by the interaction of bacterial subcapsular components and bone marrow-derived DC (likely Toll-like) receptors acting in a myeloid differentiation factor 88-dependent manner. In this regard, heavy polysaccharide encapsulation interferes with both DC maturation and apoptosis induction. In contrast, neither CD95/CD95 ligand interactions nor TNF-α appear to play a role in the delayed onset of apoptosis. These data are the first to define two mechanistically distinct pathways of DC apoptosis induction in response to an extracellular bacterium that likely have important consequences for the establishment of antibacterial immunity.
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影响因子：
4.4
作者：
Lina Lu;S. Qian;P. Hershberger;W. Rudert;David H. Lynch;A. Thomson
通讯作者：
Lina Lu;S. Qian;P. Hershberger;W. Rudert;David H. Lynch;A. Thomson
DOI：
10.1073/pnas.96.5.2396
发表时间：
1999-03-02
影响因子：
11.1
作者：
Hersh, D;Monack, DM;Zychlinsky, A
通讯作者：
Zychlinsky, A
影响因子：
15.9
作者：
Leib, SL;Kim, YS;Tauber, MG
通讯作者：
Tauber, MG
影响因子：
16
作者：
Medzhitov, R;Preston-Hurlburt, P;Janeway, CA
通讯作者：
Janeway, CA
DOI：
10.1073/pnas.92.13.5965
发表时间：
1995-06-20
影响因子：
11.1
作者：
GOTTLIEB, RA;GIESING, HA;BABIOR, BM
通讯作者：
BABIOR, BM