Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis
Recruitment of macrophages and polymorphonuclear leukocytes in Lyme carditis
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DOI：
10.1128/iai.00685-06
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Brown, Charles R.
中科院分区：
文献类型：
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作者：
Montgomery, Ruth R.;Booth, Carmen J.;Brown, Charles R.
莱姆关节炎由螺旋体伯氏疏螺旋体引起，可能会复发或长期存在，而莱姆心脏炎则大多不会复发。关节炎和心脏炎之间的一个显着区别是这些病变中吞噬细胞的差异表现：多形核白细胞（PMN）在关节中更为普遍，而巨噬细胞在心脏病变中占主导地位。我们之前已经展示了中性粒细胞和巨噬细胞清除伯氏疏螺旋体的效率差异，现在我们研究细胞水平上的这些功能差异是否可能导致观察到的器官特异性发病机制的差异。当我们用螺旋体感染缺乏中性粒细胞趋化因子受体的小鼠（CXCR2（-/-）小鼠）时，我们在关节中检测到较少的中性粒细胞和较不严重的关节炎。在这里，我们研究了巨噬细胞趋化因子受体 CCR2 缺失对耐药 (C57BL/6J [B6]) 和敏感 (C3H/HeJ [C3H]) 品系小鼠莱姆心脏炎的发生和消退的影响。在 B6 CCR2(-/-) 小鼠中，尽管心脏炎症较轻，但与野生型 (WT) 小鼠相比，我们检测到伯氏疏螺旋体的负担增加，表明在缺乏巨噬细胞的情况下清除率降低。相比之下，C3H CCR2(-/-) 小鼠在疾病高峰期和消退期间具有严重的炎症，但与 WT OH 小鼠相比，伯氏疏螺旋体负荷减少。对受感染心脏的组织病理学检查显示，受感染的 C3H CCR2(-/-) 动物中 PMN 的存在增加，表明受感染的 C3H CCR2(-/-) 小鼠心脏中伯氏疏螺旋体清除的补偿机制。与 WT OH 小鼠相比，CCR2(-/-) 更有效地从心脏清除伯氏疏螺旋体，这表明 C3H 小鼠中巨噬细胞的募集或功能存在天然缺陷，这可能导致该菌株对伯氏疏螺旋体感染的敏感性。
Lyme arthritis, caused by the spirochete Borrelia burgdorferi, can be recurrent or prolonged, whereas Lyme carditis is mostly nonrecurring. A prominent difference between arthritis and carditis is the differential representation of phagocytes in these lesions: polymorphonuclear leukocytes (PMN) are more prevalent in the joint, and macrophages predominate in the heart lesion. We have previously shown differential efficiency of B. burgdorferi clearance by PMN and macrophages, and we now investigate whether these functional differences at the cellular level may contribute to the observed differences in organ-specific pathogenesis. When we infected mice lacking the neutrophil chemokine receptor (CXCR2(-/-) mice) with spirochetes, we detected fewer PMN in joints and less-severe arthritis. Here we have investigated the effects of the absence of the macrophage chemokine receptor CCR2 on the development and resolution of Lyme carditis in resistant (C57BL/6J [B6]) and sensitive (C3H/HeJ [C3H]) strains of mice. In B6 CCR2(-/-) mice, although inflammation in hearts is mild, we detected an increased burden of B. burgdorferi compared to that in wild-type (WT) mice, suggesting reduced clearance in the absence of macrophages. In contrast, C3H CCR2(-/-) mice have severe inflammation but a decreased B. burgdorferi burden compared to that in WT OH mice both at peak disease and during resolution. Histopathologic examination of infected hearts revealed that infected C3H CCR2(-/-) animals have an increased presence of PMN, suggesting compensatory mechanisms of B. burgdorferi clearance in the hearts of infected C3H CCR2(-/-) mice. The more efficient clearance of B. burgdorferi from hearts by CCR2(-/-) versus WT OH mice suggests a natural defect in the recruitment or function of macrophages in C3H mice, which may contribute to the sensitivity of this strain to B. burgdorferi infection.