Department of Oral Biology, University of Medicine and Dentistry of New Jersey, New Jersey Dental School, Newark, New Jersey, United States of America.
PLoS One. 2013 Jul 23;8(7):e69382. doi: 10.1371/journal.pone.0069382. Print 2013.
Our aim was to explore the effects of Cytolethal Distending toxin (Cdt) in a well established rat model of periodontal disease where leukotoxin (LtxA) was thought to have no known effect. In vitro studies, were used to assess CdtB activity using Aa Leukotoxin as a negative control. These studies showed that both CdtB and LtxA (unexpectedly) exerted significant effects on CD4(+) T cells. As a result we decided to compare the effects of these two prominent Aa virulence factors on bone loss using our rat model of Aa-induced periodontitis. In this model, Aa strains, mutant in cdtB and ltxA, were compared to their parent non-mutant strains and evaluated for colonization, antibody response to Aa, bone loss and disease. We found that bone loss/disease caused by the ltxA mutant strain, in which cdtB was expressed, was significantly less (p<0.05) than that due to the wild type strain. On the other hand, the disease caused by cdtB mutant strain, in which ltxA was expressed, was not significantly different from the wild type strain. This data indicates that Aa LtxA exerts a greater effect on bone loss than Cdt in this rat model of periodontal disease and supports the utility of this model to dissect specific virulence factors as they relate to immunopathology in studies of Aa-induced disease.
我们的目的是在牙周病的大鼠模型中探索细胞致死扩张毒素（Cdt）的作用，因为白细胞毒素（LtxA）被认为没有已知的影响。体外研究用于使用 Aa 白细胞毒素作为阴性对照来评估 CdtB 活性。这些研究表明，CdtB 和 LtxA（出人意料地）对 CD4(+)T 细胞都有显著影响。因此，我们决定使用我们的 Aa 诱导牙周炎大鼠模型比较这两种主要 Aa 毒力因子对骨丢失的影响。在该模型中，比较了 cdtB 和 ltxA 突变的 Aa 菌株与其亲本非突变菌株，并评估了它们的定植、对 Aa 的抗体反应、骨丢失和疾病。我们发现，表达 cdtB 的 ltxA 突变菌株引起的骨丢失/疾病明显减少（p<0.05）比野生型菌株。另一方面，表达 ltxA 的 cdtB 突变菌株引起的疾病与野生型菌株无显著差异。该数据表明，在该牙周病大鼠模型中，与 Cdt 相比，LtxA 对骨丢失的影响更大，并支持该模型在研究 Aa 诱导疾病时分离特定毒力因子与免疫病理学的相关性。
