Differential response of respiratory dendritic cell subsets to influenza virus infection

Differential response of respiratory dendritic cell subsets to influenza virus infection
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DOI:
10.1128/jvi.02367-07
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发表时间:
2008-05-01
影响因子:
5.4
通讯作者:
Braciale, Thomas J.
Braciale, Thomas J.
中科院分区:
医学2区
文献类型:
--
作者:
Hao, Xueli;Kim, Taeg S.;Braciale, Thomas J.

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被引文献

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树突状细胞(DC)被认为在对感染(包括呼吸道感染)的先天和适应性免疫反应的启动中起重要作用,其中呼吸道DC (RDC)发挥这一作用。在本报告中,我们检测了离体小鼠RDC对流感病毒感染的敏感性,以及感染后多重感染(multiplicity of infection, MOI)对共刺激配体上调和炎症细胞因子/趋化因子产生的影响。我们发现流感病毒感染RDC的效率随着moi的增加而增加。此外,不同的RDC亚群在对流感病毒感染的易感性和共刺激配体表达的幅度/速度上存在差异。对CD11c阳性(CD11c(+)) RDC的进一步表征显示,可识别的RDC亚群对感染的易感性不同,CD11c(+) CD103(+) DC表现出最大的易感性,CD11c(+) CD11b(hi) DC表现出中等易感性,CD11c(+) B220(+)浆细胞样DC (pDC)表现出最低的易感性。对这些RDC亚群对流感病毒的体内易感性的伴随分析揭示了相应的感染模式。在流感病毒感染的体外反应中,三个RDC亚群表现出不同的细胞因子/趋化因子产生模式:pDC是大多数细胞因子的主要产生者,而CD103(+) DC和CD11b(hi) DC在流感病毒感染反应中产生小鼠趋化因子CXCL1 (KC)、白细胞介素12p40和RANTES水平升高。我们的研究结果表明,RDC是流感病毒感染的靶点,不同的RDC亚群对感染的易感性和反应不同。
Dendritic cells (DC) are believed to play an important role in the initiation of innate and adaptive immune responses to infection, including respiratory tract infections, where respiratory DC (RDC) perform this role. In this report, we examined the susceptibilities of isolated murine RDC to influenza virus infection in vitro and the effect of the multiplicity of infection (MOI) on costimulatory ligand upregulation and inflammatory cytokine/chemokine production after infection. We found that the efficiency of influenza virus infection of RDC increased with increasing MOIs. Furthermore, distinct subpopulations of RDC differed in their susceptibilities to influenza virus infection and in the magnitude/tempo of costimulatory ligand expression. Additional characterization of the CD11c-positive (CD11c(+)) RDC revealed that the identifiable subsets of RDC differed in susceptibility to infection, with CD11c(+) CD103(+) DC exhibiting the greatest susceptibility, CD11c(+) CD11b(hi) DC exhibiting intermediate susceptibility, and CD11c(+) B220(+) plasmacytoid DC (pDC) exhibiting the least susceptibility to infection. A companion analysis of the in vivo susceptibilities of these RDC subsets to influenza vir-us revealed a corresponding infection pattern. The three RDC subsets displayed different patterns of cytokine/chemokine production in response to influenza virus infection in vitro: pDC were the predominant producers of most cytokines examined, while CD103(+) DC and CD11b(hi) DC produced elevated levels of the murine chemokine CXCL1 (KC), interleukin 12p40, and RANTES in response to influenza virus infection. Our results indicate that RDC are targets of influenza virus infection and that distinct RDC subsets differ in their susceptibilities and responses to infection.