Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi
Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi
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DOI：
10.1038/labinvest.3700177
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发表时间：
2004-11-01
影响因子：
5
通讯作者：
Pachner, AR
中科院分区：
文献类型：
--
作者：
Cadavid, D;Bai, YH;Pachner, AR
为了研究莱姆病非人灵长类动物（NHP）模型的心脏受累，我们用针接种了39只成年恒河猴（Macaca mulatta）的伯氏疏螺旋体狭义菌株N40（BbN 40（N = 22，14例免疫活性（IC），7例永久性免疫抑制（IS），4例一过性免疫抑制（TISP））或蜱叮咬（N = 4，所有TISP）或菌株297（Bb 297）（N = 2 IS），或与B。793（N = 2，TISP）或Pli（N = 2，TISP）。五个未感染的NHP被用作对照。在接种后2 - 32个月尸检时取出心脏和主动脉，通过（1）H&E和三色染色;（2）免疫组织化学和数字图像分析;（3）蛋白质印迹光密度测定;和（4）TaqMan RT-PCR研究感染和炎症。所有接种BbN 40的NHP在尸检时均被感染并显示心脏炎。主要细胞为T细胞、浆细胞和巨噬细胞。心脏中IgG和IgM的增加与免疫抑制无关。B细胞趋化因子BLC在IS-NHP中显著增加。TISP和IS-NHP中补体膜攻击复合物（MAC）的沉积增加。在所有BbN 40接种的IS-NHP中，螺旋体负荷非常高，但在IC或TISP NHP中最小（如果有的话）。免疫双染显示BbN 40-IS NHP心脏中的许多螺旋体在其膜上具有MAC。我们认为B.伯氏症是常见的，并且可以持续多年，但是除非它们是免疫抑制的，否则是温和的。
To investigate cardiac involvement in the non-human primate (NHP) model of Lyme disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu stricto strains N40 (BbN40) by needle (N = 22, 14 immunocompetent (IC), seven permanently immunosuppressed ( IS), and four transiently immunosuppressed (TISP)) or by tick-bite ( N = 4, all TISP) or strain 297 ( Bb297) by needle ( N = 2 IS), or with B. garinii strains Pbi ( N = 4, 2 TISP and 2 IS), 793 ( N = 2, TISP) or Pli ( N = 2, TISP). Five uninfected NHPs were used as controls. Infection and inflammation was studied in the hearts and the aorta removed at necropsy 2 - 32 months after inoculation by ( 1) H&E and trichrome-staining; ( 2) immunohistochemistry and digital image analysis; ( 3) Western blot densitometry; and ( 4) TaqMan RT-PCR. All NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The predominant cells were T cells, plasma cells, and macrophages. There was increased IgG and IgM in the heart independent of immunosuppression. The B-cell chemokine BLC was significantly increased in IS-NHPs. There was increased deposition of the complement membrane attack complex ( MAC) in TISP and IS-NHPs. The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis in NHPs infected with B. burgdorferi is frequent and can persist for years but is mild unless they are immunosupressed.