Cross-reactive adaptive immune response to oral commensal bacteria results in an induction of receptor activator of nuclear factor-κB ligand (RANKL)-dependent periodontal bone resorption in a mouse model
Cross-reactive adaptive immune response to oral commensal bacteria results in an induction of receptor activator of nuclear factor-κB ligand (RANKL)-dependent periodontal bone resorption in a mouse model
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DOI：
10.1111/j.1399-302x.2007.00348.x
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Taubman, M. A.
中科院分区：
文献类型：
--
作者：
Kawai, T.;Paster, B. J.;Taubman, M. A.
简介：本研究检测了通过免疫与口腔遗传学密切相关的细菌放线杆菌（Actinobacillusactinomycetemcomitans）诱导对口腔定植的非致病性嗜肺巴斯德菌的适应性免疫应答是否会导致小鼠牙周骨丢失。伴放线菌在第30天处死动物，并进行以下测量：（i）血清免疫球蛋白G和牙龈T细胞对A.结果：用放线菌共生菌和嗜肺假单胞菌免疫小鼠，检测牙龈组织中RANKL阳性T细胞的表达，并与牙周骨丢失的发生率进行比较。伴放线菌引起血清免疫球蛋白G对29-kDa A.结果显示，与对照非免疫小鼠中的结果相比，伴随放线菌外膜蛋白（Omp 29）显示出与嗜肺假单胞菌OmpA的强交叉反应性。助理伴放线菌免疫的嗜肺假单胞菌（+）小鼠以RANKL依赖性方式发生显著的牙周骨丢失，如通过骨保护素-Fc治疗消除骨丢失所确定的。从A.伴放线菌免疫的嗜肺变形杆菌（+）小鼠对放线菌和嗜肺变形杆菌均表现出体外增殖反应。伴随放线菌和嗜肺假单胞菌抗原呈递，以及培养物上清液中可溶性RANKL的产生。双色共聚焦显微镜显示，A.结论：对口服定植的非致病性嗜肺假单胞菌的适应性免疫应答的诱导导致小鼠中RANKL依赖性牙周骨丢失。
Introduction: The present study examined whether induction of an adaptive immune response to orally colonizing non-pathogenic Pasteurella pneumotropica by immunization with the phylogenetically closely related bacterium, Actinobacillus actinomycetemcomitans, can result in periodontal bone loss in mice.Methods: BALB/c mice harboring P. pneumotropica (P. pneumotropica(+) mice) in the oral cavity or control P. pneumotropica-free mice were immunized with fixed A. actinomycetemcomitans. The animals were sacrificed on day 30, and the following measurements were carried out: (i) serum immunoglobulin G and gingival T-cell responses to A. actinomycetemcomitans and P. pneumotropica; (ii) periodontal bone loss; and (iii) identification of receptor activator of nuclear factor-kappa B ligand (RANKL) -positive T cells in gingival tissue.Results: Immunization with A. actinomycetemcomitans induced a significantly elevated serum immunoglobulin G response to the 29-kDa A. actinomycetemcomitans outer membrane protein (Omp29), which showed strong cross-reactivity with P. pneumotropica OmpA compared to results in the control non-immunized mice. The A. actinomycetemcomitans-immunized P. pneumotropica(+) mice developed remarkable periodontal bone loss in a RANKL-dependent manner, as determined by the abrogation of bone loss by treatment with osteoprotegerin-Fc. The T cells isolated from the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice showed an in vitro proliferative response to both A. actinomycetemcomitans and P. pneumotropica antigen presentation, as well as production of soluble(s)RANKL in the culture supernatant. Double-color confocal microscopy demonstrated that the frequency of RANKL(+) T cells in the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice was remarkably elevated compared to control mice.Conclusion: The induction of an adaptive immune response to orally colonizing non-pathogenic P. pneumotropica results in RANKL-dependent periodontal bone loss in mice.