Cardiac apoptosis in severe relapsing fever borreliosis
Cardiac apoptosis in severe relapsing fever borreliosis
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DOI：
10.1128/iai.73.11.7669-7676.2005
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发表时间：
2005-11-01
影响因子：
3.1
通讯作者：
Cadavid, D
中科院分区：
文献类型：
--
作者：
Londoño, D;Bai, YH;Cadavid, D
先前的研究表明，当免疫反应受损时，实验性莱姆病和回归热疏螺旋体病期间心脏会遭受严重损伤（D. Cadavid、Y. Bai、E. Hodzic、K. Narayan、S. W. Barthold 和 A. R. Pachner, Lab. Investig. 84:1439-1450, 2004；D. Cadavid、T. O'Neill、H. Schaefer, 11. Pachner，Lab. 80：1043-1054，2000；和 D. Cadavid，D. D. Thomas，R. Crawley，和 A. G. Barbour，J. Exp Med 179：631-642。为了研究伯氏疏螺旋体心脏炎的心脏损伤，我们使用了持续感染回归热病原疏螺旋体的同基因血清型的抗体缺陷小鼠。我们通过 TaqMan 逆转录 PCR 和免疫组织化学 (IHC) 研究了接种后 1 至 2 个月的心脏感染情况，并通过苏木精、伊红和三色染色、IHC 和原位杂交 (ISH) 研究了炎症。我们通过末端转移酶介导的 DNA 缺口末端标记测定研究细胞凋亡，并通过 RNase 保护测定、免疫荧光和免疫印迹测量细胞凋亡分子的表达。所有抗体缺陷小鼠（但没有免疫活性的对照小鼠）都出现了持续的心脏感染。感染血清型2的抗体缺陷小鼠比感染血清型1的小鼠有更严重的心脏感染和损伤。心脏基部和心包周围的损伤更为严重，对应于活化巨噬细胞明显浸润和白细胞介素 6 (IL-6) 上调的部位。受感染的心脏显示出巨噬细胞和心肌细胞凋亡的证据，以及 caspase 的显着上调，尤其是 caspase-1。我们得出结论，回归热疏螺旋体的持续感染会导致心肌细胞显着损失，并与活化巨噬细胞的显着浸润、IL-6 上调、caspase-1 诱导和细胞凋亡相关。
Previous studies revealed that the heart suffers significant injury during experimental Lyme and relapsing fever borreliosis when the immune response is impaired (D. Cadavid, Y. Bai, E. Hodzic, K. Narayan, S. W. Barthold, and A. R. Pachner, Lab. Investig. 84:1439-1450, 2004; D. Cadavid, T. O'Neill, H. Schaefer, and A. 11. Pachner, Lab. Investig. 80:1043-1054,2000; and D. Cadavid, D. D. Thomas, R. Crawley, and A. G. Barbour, J. Exp. Med. 179:631-642, 1994). To investigate cardiac injury in borrelia carditis, we used antibody-deficient mice persistently infected with isogenic serotypes of the relapsing fever agent Borrelia turicatae. We studied infection in hearts I to 2 months after inoculation by TaqMan reverse transcription-PCR and immunohistochemistry (IHC) and inflammation by hematoxylin and eosin and trichrome staining, IHC, and in situ hybridization (ISH). We studied apoptosis by terminal transferase-niediated DNA nick end labeling assay and measured expression of apoptotic molecules by RNase protection assay, immunofluorescence, and immunoblot. All antibody-deficient mice, but none of the immunocompetent controls, developed persistent infection of the heart. Antibody-deficient mice infected with serotype 2 had more severe cardiac infection and injury than serotype 1-infected mice. The injury was more severe around the base of the heart and pericardium, corresponding to sites of marked infiltration by activated macrophages and upregulation of interleukin-6 (IL-6). Infected hearts showed evidence of apoptosis of macrophages and cardiomyocytes as well as significant upregulation of caspases, most notably caspase-1. We conclude that persistent infection with relapsing fever borrelias causes significant loss of cardiomyocytes associated with prominent infiltration by activated macrophages, upregulation of IL-6, induction of caspase-1, and apoptosis.