Pantelic Milica, Kim Young-June, Bolland Silvia, Chen Ines, Shively John, Chen Tie
Department of Microbiology and Immunology, Division of Infectious Diseases, Walther Oncology Center, Indiana University School of Medicine, MS415E, 635 Barnhill Dr., Indianapolis, Indiana 46202-5120, USA.
Infect Immun. 2005 Jul;73(7):4171-9. doi: 10.1128/IAI.73.7.4171-4179.2005.
Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for gonorrhea, can cause repeated infections. During and after gonococcal infection, local and systemic antigonococcal antibody levels are low. These clinical data indicate the possibility that GC may suppress immune responses during infection. Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a), a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory signals. In the present study, human B cells were activated by interleukin-2 to express CEACAM1 and then stimulated to secrete antibodies and simultaneously coincubated with Opa- and OpaI GC of strain MS11. Our results show that this OpaI GC has the ability to inhibit antibody production. The interaction of GC and CEACAM1 with human peripheral B cells also results in induction of cell death. The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP-1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody production by killing CEACAM1-expressing B cells.
淋病奈瑟菌细胞(淋球菌[GC])是淋病的病原体,可导致反复感染。在淋球菌感染期间及之后,局部和全身抗淋球菌抗体水平较低。这些临床数据表明,GC在感染期间可能会抑制免疫反应。癌胚抗原相关细胞黏附分子1(CEACAM1或CD66a)是GC不透明(Opa)蛋白的受体,已被证明可介导抑制性信号。在本研究中,人B细胞通过白细胞介素-2激活以表达CEACAM1,然后刺激其分泌抗体,并同时与MS11菌株的Opa和OpaI GC共同孵育。我们的结果表明,这种OpaI GC具有抑制抗体产生的能力。GC和CEACAM1与人外周B细胞的相互作用还会导致细胞死亡。在DT40 B细胞中也观察到了相同的结果。这种由CEACAM1促进的细胞死亡途径不涉及抑制性信号或酪氨酸磷酸酶SHP-1和SHP-2,但在DT40细胞中依赖于布鲁顿酪氨酸激酶。我们的结果表明,淋病奈瑟菌具有通过杀死表达CEACAM1的B细胞来抑制抗体产生的能力。