Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model

Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model
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DOI:
10.1046/j.1365-2249.2002.01852.x
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发表时间:
2002-05-01
影响因子:
4.6
通讯作者:
Seymour, GJ
Seymour, GJ
中科院分区:
医学3区
文献类型:
--
作者:
Gemmell, E;Bird, PS;Seymour, GJ

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测定了仅用盐水、活的具核梭杆菌 ATCC 25586、活的牙龈卟啉单胞菌 ATCC 33277、具核梭杆菌、随后的牙龈卟啉单胞菌和具核梭杆菌、随后的具核梭杆菌免疫的五组 BALB/c 小鼠的 T 细胞细胞因子谱和特异性血清抗体水平。通过双色流式细胞术检查脾 CD4 和 CD8 细胞的胞浆内白细胞介素 (IL)-4、干扰素 (IFN)-γ 和 IL-10 以及血清抗 F 的水平。 nucleatum 和抗 P.通过 ELISA 测定牙龈杆菌抗体。所有组均表现出 Th1 和 Th2 反应,虽然与其他接种细菌的组相比,单独注射具核梭杆菌的小鼠中细胞因子阳性 T 细胞的百分比略低,但在接种这两种生物体的两组中,具核梭杆菌对牙龈卟啉单胞菌诱导的 T 细胞产生细胞因子没有影响。然而,细胞因子阳性CD8细胞的百分比通常显着高于CD4细胞。单独用具核梭杆菌免疫的小鼠血清中抗具核梭杆菌抗体水平较高,牙龈卟啉单胞菌抗体水平极低,而单独注射牙龈卟啉单胞菌的小鼠则产生抗具核杆菌抗体。主要是牙龈炎抗体。虽然注射具核球菌后注射牙龈卟啉单胞菌的小鼠中抗具核球菌抗体水平与单独注射具核杆菌的小鼠相同,但针对牙龈卟啉单胞菌的抗体水平非常低。相比之下,注射牙龈卟啉单胞菌,然后注射具核杆菌的小鼠产生了相同水平的两种抗-牙龈卟啉单胞菌。牙龈炎和抗具核 F 抗体,尽管其水平分别低于用细菌免疫的其他三组。还测定了抗伴放线放线杆菌、福赛拟杆菌和中间普雷沃氏菌的血清抗体水平,发现可以忽略不计。总之,具核梭菌免疫不影响脾 T 细胞对牙龈卟啉单胞菌的细胞因子反应。然而,在具核梭菌免疫之前接种具核梭菌几乎完全抑制了抗牙龈梭菌抗体的产生,而在具核梭菌之前注射牙龈梭菌则证明了牙龈梭菌对具核梭菌抗体产生的部分抑制作用。这些结果对于人类牙周病的意义很难确定。然而,它们可以部分解释不同个体对牙龈卟啉单胞菌的不同反应,这些个体之前可能接触过具核梭菌,也可能没有接触过具核梭菌。最后,结果表明牙龈卟啉单胞菌和具核梭菌不会诱导与其他口腔微生物产生交叉反应性抗体。
T cell cytokine profiles and specific serum antibody levels in five groups of BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC 25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P. gingivalis and P. gingivalis followed by F nucleatum were determined. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA. Both Th1 and Th2 responses were demonstrated by all groups, and while there were slightly lower percentages of cytokine positive T cells in mice injected with F. nucleatum alone compared with the other groups immunized with bacteria., F nucleatum had no effect on the T cell production of cytokines induced by P gingivalis in the two groups immunized with both organisms. However, the percentages of cytokine positive CD8 cells were generally significantly higher than those of the CD4 cells. Mice immunized with F nucleatum alone had high levels of serum anti-E nucleatum antibodies with very low levels of P. gingivalis antibodies, whereas mice injected with P gingivalis alone produced anti-P. gingivalis antibodies predominantly. Although the levels of anti-E nucleatum antibodies in mice injected with E nucleatum followed by P. gingivalis were the same as in mice immunized with F nucleatum alone, antibody levels to P. gingivalis were very low. In contrast, mice injected with P. gingivalis followed by F nucleatum produced equal levels of both anti-P. gingivalis and anti-F nucleatum antibodies, although at lower levels than the other three groups immunized with bacteria, respectively. Anti-Actinobacillus actitiomycetemcomitans, Bacteroides forsythus and Prevotella intermedia serum antibody levels were also determined and found to be negligible. In conclusion, F nucleatum immunization does not affect the splenic T cell cytokine response to P. gingivalis. However, F nucleatum immunization prior to that of P. gingivalis almost completely inhibited the production of anti-P gingivalis antibodies while P. gingivalis injection before F. nucleatum demonstrated a partial inhibitory effect by P. gingivalis on antibody production to F. nucleatum. The significance of these results with respect to human periodontal disease is difficult to determine. However, they may explain in part differing responses to P. gingivalis in different individuals who may or may not have had prior exposure to F. nucleatum. Finally, the results suggested that P. gingivalis and F. nucleatum do not induce the production of cross-reactive antibodies to other oral microorganisms.