Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin-6 secretion via toll-like receptor 2
Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin-6 secretion via toll-like receptor 2
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DOI：
10.1128/iai.00949-07
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Giambartolomei, Guillermo H.
中科院分区：
文献类型：
--
作者：
Barrionuevo, Paula;Cassataro, Juliana;Giambartolomei, Guillermo H.
目前尚不清楚使牛种布鲁氏菌在巨噬细胞内长期存活并避免产生主要组织相容性复合体II类（MHC-II）限制性γ干扰素（IFN-γ）的CD 4（+）T淋巴细胞的免疫监视的策略。我们在这里报告，感染的THP-1细胞与B。流产抑制MHC-II分子的表达和抗原（Ag）加工。热灭活B。流产杆菌（HKBA）也诱导了这两种现象，表明细菌活力的独立性和细菌结构组分的参与。因此，外膜蛋白19（Omp 19），一个典型的B。流产脂蛋白，抑制MHC-Ⅱ表达和Ag加工的程度与HKBA相同。此外，模拟蛋白质脂质部分结构的合成脂六肽也抑制MHC-II表达，表明任何布鲁氏菌脂蛋白都可以下调MHC-II表达和Ag加工。HKBA或脂化Omp 19（L-Omp 19）对MHC-II表达和Ag加工的抑制依赖于Toll样受体2，并由白细胞介素-6介导。HKBA或L-Omp 19也抑制人单核细胞的MHC-Ⅱ表达和Ag加工。此外，暴露于合成的脂六肽抑制了布鲁氏菌感染患者外周血单个核细胞的Ag特异性T细胞增殖和IFN-γ产生。总之，这些结果表明存在一种机制，通过该机制B.流产可能会阻止T细胞的识别，以逃避宿主免疫并建立慢性感染。
The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-gamma)-producing CD4(+) T lymphocytes are poorly understood. We report here that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen (Ag) processing. Heat-killed B. abortus (HKBA) also induced both these phenomena, indicating the independence of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation and IFN-gamma production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection.