Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses
Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses
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DOI：
10.1007/s00430-010-0173-y
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发表时间：
2011-02-01
影响因子：
5.4
通讯作者：
Cinatl, Jindrich, Jr.
中科院分区：
文献类型：
--
作者：
Geiler, Janina;Michaelis, Martin;Cinatl, Jindrich, Jr.
甲型流感病毒感染巨噬细胞和病毒诱导的促炎基因表达被认为与甲型流感病毒引起的疾病的严重程度有关。虽然有一些关于甲型流感病毒感染的巨噬细胞产生细胞因子的数据，但目前认为，系统比较病毒类型与人类（H1N1/2009大流行性流感、季节性H1N1、季节性H3N2、高致病性禽流感H5N1）的促炎潜力高度相关，并且缺乏相关的潜在细胞信号事件。在这里，我们发现人类单核细胞来源的巨噬细胞感染大流行性H1N1/2009 (A/HH/01/2009)，季节性H1N1/1999 (A/New Caledonia/20/99)，季节性H3N2/2004 （A/California/7/2004）或高致病性H5N1/2004 （A/Thailand/1(Kan-1)/04）的感染率相似。然而，与H3N2/2004或H5N1/2004相比，所调查的H1N1毒株导致细胞凋亡延迟和减少。此外，人类巨噬细胞感染H3N2/2004或H5N1/2004病毒，但不感染H1N1病毒，与显著的促炎细胞因子产生和相关丝裂原激活的蛋白激酶途径的激活相关，这可以通过p38、JNK和erk1 /2的磷酸化来证明。这些发现与临床观察结果一致，表明与H1N1/2009大流行性流感或季节性H1N1感染个体相比，H3N2或h5n1感染患者的疾病严重程度增强。
Influenza A virus infection of macrophages and virus-induced pro-inflammatory gene expression are regarded to contribute to severity of influenza A virus-caused diseases. Although some data are available on cytokine production by influenza A virus-infected macrophages, systematic comparisons of the virus types are currently considered to be of high relevance in humans (pandemic H1N1/2009, seasonal H1N1, seasonal H3N2, highly pathogenic avian influenza H5N1) on pro-inflammatory potential, and relevant underlying cellular signalling events are missing. Here, we show that the infection of human monocyte-derived macrophages with pandemic H1N1/2009 (A/HH/01/2009), seasonal H1N1/1999 (A/New Caledonia/20/99), seasonal H3N2/2004 (A/California/7/2004) or highly pathogenic H5N1/2004 (A/Thailand/1(Kan-1)/04) results in similar infection rates. However, the investigated H1N1 strains caused delayed and decreased apoptosis in comparison with H3N2/2004 or H5N1/2004. Moreover, human macrophage infection with H3N2/2004 or H5N1/2004 but not with H1N1 viruses was associated with pronounced pro-inflammatory cytokine production and activation of relevant mitogen-activated protein kinase pathways as indicated by phosphorylation of p38, JNK and ERK 1/2. These findings are in line with clinical observations indicating enhanced disease severity in H3N2- or H5N1-infected patients compared to individuals infected with pandemic H1N1/2009 or seasonal H1N1.