Subversion of pulmonary dendritic cell function by paramyxovirus infections.

Subversion of pulmonary dendritic cell function by paramyxovirus infections.
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DOI:
10.4049/jimmunol.0802262
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发表时间:
2009-03-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Garofalo RP
Garofalo RP
中科院分区:
其他
文献类型:
--
作者:
Guerrero-Plata A;Kolli D;Hong C;Casola A;Garofalo RP

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由副粘病毒、人偏肺病毒(hMPV)和呼吸道合胞病毒(RSV)引起的下呼吸道感染的特征在于短暂的病毒特异性免疫和通常长期的气道发病率,这两者都可能是这些感染后肺的抗原呈递功能改变的结果。在这项研究中,我们调查了hMPV和RSV实验感染是否改变了树突状细胞(DC)亚群的表型和功能,这些亚群被招募到肺部。肺DC运输的表征表明,在hMPV和RSV感染后,浆细胞样DC(pDC)、常规DC(cDC)和产生干扰素的杀伤DC(IKDC)向肺和引流淋巴结的差异募集。肺DC的体外感染表明,在pDC中,IFN-α、TNF-α和CCL 5的产生仅由hMPV诱导,而CCL 3和CCL 4由两种病毒诱导。在cDC中,hMPV和RSV诱导了类似的细胞因子库,除了IFN-β,其不由RSV诱导。在体内hMPV或RSV感染后,肺pDC的功能改变,因为我们证明肺pDC响应于TLR 9激动剂产生IFN-α以及其他细胞因子(包括IL-6、TNF-α、CCL 2、CCL 3和CCL 4)的能力降低。此外,我们观察到感染小鼠的cDC向CD 4 + T细胞呈递Ag的能力受损,这种影响持续到感染的急性期之后。我们的研究结果表明,急性副粘病毒感染可以改变肺DC的长期免疫功能。
Lower respiratory tract infections caused by the paramyxoviruses human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are characterized by short-lasting virus-specific immunity and often long term airway morbidity, both of which may be the result of alterations in the antigen presenting function of the lung which follow these infections. In this study, we investigated whether hMPV and RSV experimental infections alter the phenotype and function of dendritic cells (DC) subsets which are recruited to the lung. Characterization of lung DC trafficking demonstrated a differential recruitment of plasmacytoid DC (pDC), conventional DC (cDC) and interferon-producing killer DC (IKDC) to the lung and draining lymph nodes after hMPV and RSV infection. In vitro infection of lung DC indicated that in pDC, production of IFN-α, TNF-α, and CCL5 was induced only by hMPV while CCL3 and CCL4 were induced by both viruses. In cDC, a similar repertoire of cytokines was induced by hMPV and RSV, except for IFN-β, which was not induced by RSV. The function of lung pDC was altered following hMPV or RSV infection in vivo, as we demonstrated a reduced capacity of lung pDC to produce IFN-α as well as other cytokines including IL-6, TNF-α, CCL2, CCL3 and CCL4 in response to TLR9 agonist. Moreover, we observed an impaired capacity of cDC from infected mice to present Ag to CD4+ T cells, an effect that lasted beyond the acute phase of infection. Our findings suggest that acute paramyxovirus infections can alter the long term immune function of pulmonary DC.
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