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早期HIV-1感染者單核細胞對TLR配體反應性研究
來源: | 作者: | 發布時間:2014-4-15 17:00:59

早期HIV-1感染者單核細胞對TLR配體反應性研究
梁華1,沈弢2
基金項目:教育部博士點基金(20100001120047);國家自然科學基金項目(81271826, 31100126) 作者簡介:梁華,女,醫學博士,主要研究方向為病毒免疫學 通信聯系人:沈弢(1971-)男,副教授,主要研究方向為HCV的病毒學和免疫學. 

(1. 中國疾病預防控制中心性病艾滋病預防控制中心病毒免疫室; 5 2. 北京大學醫學部基礎醫學院病原生物學系)
摘要:目的 探討HIV-1早期感染者體內單核細胞的成熟狀態和對TLR配體的反應特點,了解HIV-1感染早期單核細胞功能狀態和與疾病進展狀態的相關性。 方法 選取35例HIV-1早期感染者,采血分離PBMC后純化出單核細胞,流式細胞術檢測單核細胞表面活10 化/抑制分子表達。用LPS和Pam3CSK4分別刺激單核細胞,培養20h后,流式細胞術檢測單核細胞表面活化/抑制分子表達,ELISA方法檢測培養上清中促炎細胞因子IL-1β,TNF-α,IL-6的分泌水平。 結果 HIV-1早期感染者,單核細胞表面活化分子CD80、CD86、CD40和抑制分子PD-L1表達均升高(除CD86 P=0.01外,P均<0.001),CD40表達水平與血漿病毒載量正相關(P<0.001,R=0.553)。單核細胞受LPS和Pam3CSK4刺激后,活化15 成熟能力降低,HLA-DR、CD80、CD86、PD-L1表達增加均較健康對照低(P<0.001),而促炎細胞因子TNF-α(LPS:P=0.004,Pam3CSK4:P=0.012)和IL-6分泌(LPS:P=0.006)增加。 結論 在HIV-1感染早期,單核細胞即處于免疫活化狀態,受TLR配體刺激后促炎細胞因子分泌增加可能與HIV-1感染后的微生物移位和免疫活化相關。
關鍵詞:人類免疫缺陷病毒;單核細胞;TLR2;TLR4 20
中圖分類號:[R394.5]
Responses of Monocytes to TLR Ligands in Primary HIV-1 Infection
Hua Liang1, Tao Shen2 25
(1. National center for HIV/AIDS control and prevention, China CDC; 2. Department of Microbiology, Peking University Health Science Center)
Abstract: Objective To explore the maturation status of monocytes and the responses of monocytes to TLR ligands in primary HIV-1 infection, and to understand the association between functional status of monocytes and disease progression in primary HIV-1 infection. Methods 30 Monocytes were isolated from PBMC of 35 primary HIV-1 infected subjects. Activate/inhibitory markers expression on monocytes were analyzed by flow cytometry. Monocytes were stimulated with LPS and Pam3CSK4 and cultured for 20h. Activate/inhibitory markers expression on monocytes were analyzed by flow cytometry and secretions of proinflammatory cytokines by stimulated monocytes were detected by ELISA. Results In primary HIV-1 infection, activate 35 markers CD80, CD86, CD40, and inhibitory marker PD-L1 expression on monocytes were increased (P<0.001 except for CD86 P=0.01). CD40 expression was positively correlated with plasma viral load (P<0.001,R=0.553). After stimulated with LPS and Pam3CSK4, the increases of HLA-DR, CD80, CD86, and PD-L1 expression were lower in primary HIV-1 infection compared with healthy controls (P<0.001),and secretions of proinflammatory cytokines TNF-α40 (LPS:P=0.004,Pam3CSK4:P=0.012)and IL-6(LPS:P=0.006)were enhanced in monocytes of primary HIV-1 infection. Conclusion In primary HIV-1 infection, monocytes were activated and secreted higher levels of proinflammatory cytokines after TLR ligands stimulation, suggesting a possible role of monocytes in microbial translocation and immune activation in HIV-1 infection.
Key words: human immunodeficiency virus; monocytes; Toll like receptor 2; Toll like receptor 4

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