BORDETELLA-PERTUSSIS INDUCES APOPTOSIS IN MACROPHAGES - ROLE OF ADENYLATE CYCLASE-HEMOLYSIN
BORDETELLA-PERTUSSIS INDUCES APOPTOSIS IN MACROPHAGES - ROLE OF ADENYLATE CYCLASE-HEMOLYSIN
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DOI：
10.1128/iai.61.10.4064-4071.1993
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发表时间：
1993-10-01
影响因子：
3.1
通讯作者：
GUISO, N
中科院分区：
文献类型：
--
作者：
KHELEF, N;ZYCHLINSKY, A;GUISO, N
百日咳的病原体——百日咳博德泰拉，最近在体外被证明能进入上皮细胞和巨噬细胞并存活。在本研究中，我们发现百日咳对单核巨噬细胞系J774A.1细胞和小鼠肺泡巨噬细胞具有细胞毒性。我们证明百日咳介导的细胞毒性通过细胞凋亡发生，如核形态的变化和宿主细胞DNA断裂所示。亲本株和百日咳毒素表达缺陷的突变株能够诱导细胞凋亡，而无毒突变株或腺苷酸环化酶-溶血素缺陷突变株则没有细胞毒性。腺苷酸环化酶和溶血活性都是程序性细胞死亡所必需的。这些结果表明细胞凋亡的诱导依赖于腺苷酸环化酶-溶血素的表达。原代培养小鼠肺泡巨噬细胞感染百日咳杆菌可导致细胞凋亡，提示这一过程可能与体内相关。百日咳促进细胞死亡的能力可能对感染的开始、细菌的存活和宿主免疫反应的逃避很重要。
Bordetella pertussis, the causative agent of whooping cough, has been shown recently to enter and survive in epithelial cells and macrophages in vitro. In the present study, we show that B. pertussis is cytotoxic for J774A.1 cells, a monocyte-macrophage cell line, and for murine alveolar macrophages. We demonstrate that cell cytotoxicity mediated by B. pertussis occurred through apoptosis, as shown by changes in nuclear morphology and by host cell DNA fragmentation. Parental strains and a mutant deficient in pertussis toxin expression are able to induce apoptosis, whereas avirulent mutant or adenylate cyclase-hemolysin-deficient mutants are not cytotoxic. Both adenylate cyclase and hemolytic activities are required for programmed cell death. These results show that induction of apoptosis is dependent on the expression of adenylate cyclase-hemolysin. The infection of murine alveolar macrophages in primary culture with B. pertussis leads to apoptosis, suggesting that this process might be relevant in vivo. The ability of B. pertussis to promote cell death may be important for the initiation of infection, bacterial survival, and escape of the host immune response.