WFDC1/ps20: a host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection.

WFDC1/ps20: a host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection.
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DOI:
10.1016/j.antiviral.2012.08.012
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发表时间:
2012-11
期刊:
影响因子:
7.6
通讯作者:
Fish EN
Fish EN
中科院分区:
医学2区
文献类型:
--
作者:
Rogers E;Wang BX;Cui Z;Rowley DR;Ressler SJ;Vyakarnam A;Fish EN

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► 宿主因素WFDC1/ps20影响先天免疫反应。 ► WFDC1/ps20 具有针对 MHV-1 感染的保护作用。 ► WFDC1/ps20 调节中性粒细胞反应。乳清酸性蛋白家族成员 WFDC1/ps20 是 HIV 感染的许可因素。在此,我们描述了 ps20 在限制 MHV-1 感染中的对比作用。鼻内 MHV-1 感染会导致小鼠呼吸道感染。使用 ps20 基因敲除小鼠,我们提供的证据表明,与 ps20+/+ 小鼠相比,鼻内 MHV-1 感染导致 ps20−/− 小鼠肺部病毒滴度增加。与 ps20+/+ 小鼠相比,伴随 MHV-1 感染,我们观察到 ps20−/− 小鼠浸润 BAL 的中性粒细胞数量增加,并且肺引流淋巴结中中性粒细胞的百分比增加。 MHV-1 感染后 ps20−/− 小鼠肺部中性粒细胞趋化剂 CXCL1 和 CXCL2 的基因表达水平升高。首次接触 ps20−/− 小鼠的免疫细胞特征表明,与 ps20+/+ 小鼠相比,循环中性粒细胞有所增加。 ps20+/+ 和 ps20−/− 小鼠之间的其他免疫细胞特征没有观察到显着差异。因此,我们检查了中性粒细胞的 MHV-1 感染,并提供了证据表明从 ps20−/− 小鼠中分离的中性粒细胞比从 ps20+/+ 小鼠中分离的中性粒细胞更容易受到 MHV-1 感染。这些数据表明 ps20 在调节中性粒细胞特异性趋化因子表达中的作用,从而可能调节中性粒细胞迁移,并调节中性粒细胞对 MHV-1 感染的易感性。
► Host factor, WFDC1/ps20 influences the innate immune response. ► WFDC1/ps20 confers protection against MHV-1 infection. ► WFDC1/ps20 regulates a neutrophil response. The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV infection. Herein we describe a contrasting role for ps20 in limiting MHV-1 infection. Intranasal MHV-1 infection produces a respiratory infection in mice. Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection results in increased lung viral titers in ps20−/− compared to ps20+/+ mice. Accompanying MHV-1 infection we observe an increase in the number of neutrophils infiltrating the BAL and an increase in the percentage of neutrophils in the lung draining lymph nodes of ps20−/− compared with ps20+/+ mice. Gene expression levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the lungs of ps20−/− mice post-MHV-1 infection. Characterization of the immune cell profile in naïve ps20−/− mice revealed an increase in circulating neutrophils compared to ps20+/+ mice. No notable differences in other immune cell profiles were observed between the ps20+/+ and ps20−/− mice. Accordingly, we examined MHV-1 infection of neutrophils and provide evidence that neutrophils isolated from ps20−/− mice are more susceptible to MHV-1 infection than neutrophils isolated from ps20+/+ mice. These data suggest roles for ps20 in regulating expression of neutrophil-specific chemotactic factors, thereby potentially modulating neutrophil migration, and in modulating neutrophil susceptibility to MHV-1 infection.
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