Lasky Carrie E, Pratt Carmela L, Hilliard Kinsey A, Jones John L, Brown Charles R
Department of Veterinary Pathobiology, University of Missouri , Columbia, MO , USA.
Front Immunol. 2016 Nov 3;7:468. doi: 10.3389/fimmu.2016.00468. eCollection 2016.
Infection of humans with the spirochete, , causes Lyme borreliosis and can lead to clinical manifestations such as arthritis, carditis, and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize surface lipoproteins primarily toll-like receptor (TLR)2; however, previous work has demonstrated TLR2 mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in -infected joints and hearts of C3H TLR2 mice. depletion of either CD4 or CD8 T cells reduced -induced joint swelling and lowered tissue spirochete burden, whereas depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes, and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.
人类感染螺旋体 会导致莱姆病，可引发关节炎、心肌炎和神经疾病等临床表现。小鼠实验性感染再现了其中许多症状，可作为研究疾病发病机制和免疫的模型系统。已知固有免疫会推动莱姆关节炎和心肌炎的发展，但驱动这种反应的机制仍不清楚。固有免疫细胞主要通过Toll样受体（TLR）2识别 表面脂蛋白；然而，先前的研究表明TLR2基因敲除小鼠的病情会加重且细菌负荷增加。我们证明在C3H TLR2基因敲除小鼠被 感染的关节和心脏中，CD4和CD8 T细胞浸润增加。CD4或CD8 T细胞的耗竭可减轻 诱导的关节肿胀并降低组织螺旋体负荷，而单独耗竭CD8 T细胞可降低疾病严重程度评分。莱姆关节炎的加重与滑膜细胞CXCL9产生增加相关，而CD8 T细胞耗竭可使其减少。这些结果表明，T细胞可能通过炎症反应失调和抑制细菌清除来加剧莱姆病发病机制并延长疾病缓解时间。
