Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response
Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response
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DOI：
10.1189/jlb.0604356
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发表时间：
2005-05-01
影响因子：
5.5
通讯作者：
Glickstein, L
中科院分区：
文献类型：
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作者：
Craig-Mylius, K;Weber, GF;Glickstein, L
针对细胞内病原体的经典促炎性T辅助细胞1型（T（H）1）应答包括细胞因子骨桥蛋白，其主要作用于巨噬细胞，在巨噬细胞中诱导白细胞介素（IL）-12的分泌并抑制IL-10的分泌。由于细胞介导的免疫应答在抵抗莱姆病关节炎（由细胞外病原体伯氏疏螺旋体感染的表现）中起重要作用，我们测试了骨桥蛋白可能需要诱导T（H）1应答和炎症的假设。骨桥蛋白的作用进行了测试，在体内和使用离体巨噬细胞在B6129 F3小鼠易感实验莱姆关节炎。Nice的这种遗传背景和那些完全回交到C57 BL/6，缺乏骨桥蛋白表达（spp 1（-/-）），对B敏感。burgdorferi诱导的关节炎作为同窝对照。此外，通过B的定量聚合酶链反应测量，螺旋体的数量相等。在spp 1（-/-）和B6129 F3野生型同窝仔中，burgdorferi基因recA表明感染易感性不依赖于这种细胞因子。B6129 F3亲本小鼠品系均不缺乏分泌骨桥蛋白的能力。spp 1（-/-）小鼠和对照组的免疫球蛋白G（2）滴度提示Till反应。B。Burgdorferi能够直接刺激促炎细胞因子IL-12和肿瘤坏死因子α从野生型和spp 1（-/-）巨噬细胞中的分泌。这些结果表明，骨桥蛋白在诱导细胞免疫应答细胞内病原体的能力，细胞外病原体B规避了通常的关键作用。burgdorferi直接诱导巨噬细胞产生促炎细胞因子。
A classic proinflammatory T helper cell type 1 (T(H)1) response directed against intracellnlar pathogens includes the cytokine osteopontin, which acts predominantly on macrophages, where it induces the secretion of interleukin (IL)-12 and suppresses the secretion of IL-10. As cell-mediated immune responses play an important role in the resistance to Lyme arthritis, a manifestation of infection by the extracellular pathogen Borrelia burgdorferi, we tested the hypothesis that osteopontin may be required to induce T(H)1 responses and inflammation. The role of osteopontin was tested in vivo and using ex vivo macrophages in B6129F3 mice susceptible to experimental Lyme arthritis. Nice of this genetic background and those fully backcrossed to C57BL/6, which lacked osteopontin expression (spp1(-/-)), were as susceptible to B. burgdorferi-induced arthritis as litter-mate controls. Furthermore, equal numbers of spirochetes, as measured by quantitative polymerase chain reaction of the B. burgdorferi gene recA in spp1(-/-) and B6129F3 wild-type littermates, suggested that susceptibility to infection was not dependent on this cytokine. Neither of the B6129F3 parental mouse strains lacked the ability to secrete osteopontin. spp1(-/-) mice and controls had immunoglobulin G(2) titers, suggestive of a Till response. B. burgdorferi was able to directly stimulate the secretion of the proinflammatory cytokines IL-12 and tumor necrosis factor alpha from wild-type and spp1(-/-) macrophages alike. These results indicate that the usually critical role of osteopontin in the induction of cellular immune responses to intracellular pathogens was circumvented by the ability of the extracellular pathogen B. burgdorferi to induce macrophages directly to produce proinflammatory cytokines.