Leshem Onir, Kashino Suely S, Gonçalves Reginaldo B, Suzuki Noriyuki, Onodera Masao, Fujimura Akira, Sasaki Hajime, Stashenko Philip, Campos-Neto Antonio
Department of Cytokine Biology, The Forsyth Institute, Boston, MA 02115140, USA.
Microbes Infect. 2008 May;10(6):664-72. doi: 10.1016/j.micinf.2008.03.003. Epub 2008 Mar 25.
In previous studies we showed that biasing the immune response to Porphyromonas gingivalis antigens to the Th1 phenotype increases inflammatory bone resorption caused by this organism. Using a T cell screening strategy we identified eight P. gingivalis genes coding for proteins that appear to be involved in T-helper cell responses. In the present study, we characterized the protein encoded by the PG_1841 gene and evaluated its relevance in the bone resorption caused by P. gingivalis because subcutaneous infection of mice with this organism resulted in the induction of Th1 biased response to the recombinant PG1841 antigen molecule. Using an immunization regime that strongly biases toward the Th1 phenotype followed by challenge with P. gingivalis in dental pulp tissue, we demonstrate that mice pre-immunized with rPG1841 developed severe bone loss compared with control immunized mice. Pre-immunization of mice with the antigen using a Th2 biasing regime resulted in no exacerbation of the disease. These results support the notion that selected antigens of P. gingivalis are involved in a biased Th1 host response that leads to the severe bone loss caused by this oral pathogen.
在先前的研究中，我们发现，使针对牙龈卟啉单胞菌抗原的免疫反应偏向Th1表型会增加该菌引起的炎性骨吸收。我们采用T细胞筛选策略，鉴定出8个牙龈卟啉单胞菌基因，这些基因编码的蛋白质似乎参与辅助性T细胞反应。在本研究中，我们对PG_1841基因编码的蛋白质进行了表征，并评估了其在牙龈卟啉单胞菌引起的骨吸收中的相关性，因为用该菌皮下感染小鼠会诱导对重组PG1841抗原分子产生偏向Th1的反应。采用强烈偏向Th1表型的免疫方案，随后在牙髓组织中用牙龈卟啉单胞菌进行攻击，我们证明，与对照免疫小鼠相比，用rPG1841预先免疫的小鼠出现了严重的骨质流失。使用偏向Th2的方案用该抗原预先免疫小鼠，并未导致疾病加重。这些结果支持以下观点，即牙龈卟啉单胞菌的特定抗原参与了偏向Th1的宿主反应，这种反应导致了这种口腔病原体引起的严重骨质流失。
