Bernard Quentin, Wang Zhenping, Di Nardo Anna, Boulanger Nathalie
EA7290 Virulence bactérienne précoce: groupe borréliose de Lyme, Fédération de médecine translationnelle et Faculté de Pharmacie de Strasbourg, Université de Strasbourg, Strasbourg, France.
Present address: Department of Veterinary Medicine, University of Maryland, College Park, USA.
Parasit Vectors. 2017 Jun 27;10(1):313. doi: 10.1186/s13071-017-2243-0.
Borrelia burgdorferi (sensu lato), the causative agent of Lyme borreliosis is a bacterium transmitted by hard ticks, Ixodes spp. Bacteria are injected into the host skin during the tick blood meal with tick saliva. There, Borrelia and saliva interact together with skin cells such as keratinocytes, fibroblasts, mast cells and other specific immune cells before disseminating to target organs.
To study the role of mast cells in the transmission of Lyme borreliosis, we isolated mouse primary mast cells from bone marrow and incubated them in the presence of Borrelia burgdorferi (sensu stricto) and tick salivary gland extract. We further analyzed their potential role in vivo, in a mouse model of deficient in mast cells (Kit mice).
To our knowledge, we report here for the first time the bacteria ability to induce the inflammatory response of mouse primary mast cells. We show that OspC, a major surface lipoprotein involved in the early transmission of Borrelia, induces the degranulation of primary mast cells but has a limited effect on the overall inflammatory response of these cells. In contrast, whole bacteria have an opposite effect. We also show that mast cell activation is significantly inhibited by tick salivary gland extract. Finally, we demonstrate that mast cells are likely not the only host cells involved in the early transmission and dissemination of Borrelia since the use of mast cell deficient Kit mice shows a limited impact on these two processes in the context of this mouse genetic background.
The absence of mast cells did not change the replication rate of Borrelia in the skin. However, in the absence of mast cells, Borrelia dissemination to the joints was faster. Mast cells do not control skin bacterial proliferation during primary infection and the establishment of the primary infection, as shown in the C57BL/6 mouse model studied. Nevertheless, the Borrelia induced cytotokine modulation on mast cells might be involved in long term and/or repeated infections and protect from Lyme borreliosis due to the development of a hypersensitivity to tick saliva.
莱姆病疏螺旋体（狭义）是莱姆病的病原体，由硬蜱属的蜱传播。蜱在吸血时将细菌与唾液一起注入宿主皮肤。在传播至靶器官之前，疏螺旋体和唾液会与角质形成细胞、成纤维细胞、肥大细胞等皮肤细胞以及其他特定免疫细胞相互作用。
为研究肥大细胞在莱姆病传播中的作用，我们从骨髓中分离出小鼠原代肥大细胞，并在存在狭义疏螺旋体和蜱唾液腺提取物的情况下对其进行培养。我们还在肥大细胞缺陷型（Kit小鼠）的小鼠模型中进一步分析了它们在体内的潜在作用。
据我们所知，我们首次在此报告细菌诱导小鼠原代肥大细胞炎症反应的能力。我们表明，OspC是一种参与疏螺旋体早期传播的主要表面脂蛋白，它能诱导原代肥大细胞脱颗粒，但对这些细胞的整体炎症反应影响有限。相比之下，完整细菌则有相反的作用。我们还表明，蜱唾液腺提取物可显著抑制肥大细胞的激活。最后，我们证明肥大细胞可能不是参与疏螺旋体早期传播和扩散的唯一宿主细胞，因为使用肥大细胞缺陷型Kit小鼠显示在这种小鼠遗传背景下，对这两个过程的影响有限。
肥大细胞的缺失并未改变疏螺旋体在皮肤中的复制率。然而，在没有肥大细胞的情况下，疏螺旋体向关节的扩散更快。如在研究的C57BL/6小鼠模型中所示，肥大细胞在初次感染和初次感染确立期间并不控制皮肤细菌增殖。尽管如此，疏螺旋体诱导的肥大细胞细胞因子调节可能参与长期和/或反复感染，并由于对蜱唾液产生超敏反应而预防莱姆病。
