Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology.
Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology.
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DOI：
10.1371/journal.pone.0088764
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mohapatra SS
中科院分区：
文献类型：
--
作者：
Wong TM;Boyapalle S;Sampayo V;Nguyen HD;Bedi R;Kamath SG;Moore ML;Mohapatra S;Mohapatra SS
老年人比年轻人更容易感染呼吸道合胞病毒引起的肺炎，但这种易感性背后的分子机制尚不清楚。在这项研究中，我们使用了RSV诱导的肺炎的老年小鼠模型来研究衰老如何改变肺部病理，调节抗病毒基因的表达，以及在RSV感染时炎性细胞因子的产生。幼龄(2-3月龄)和幼龄(19-21月龄)小鼠分别经鼻腔感染粘液性和非粘液性RSV毒株，进行肺组织学检查和基因表达分析。感染呼吸道合胞病毒粘液性毒株后，老年小鼠呼吸道内白细胞的渗入增加且持续时间长于年轻小鼠。Minitab析因分析确定了几个受年龄、感染和这两个因素组合影响的抗病毒基因。5个抗病毒基因的表达受年龄和感染的影响，包括促炎细胞因子IL-1β和骨桥蛋白，而AGE与15个抗病毒基因的表达有关。随着年龄的增长，抗病毒基因表达的动力学和幅度都会减弱。除了细胞因子信号和模式识别受体诱导的延迟，我们还发现TLR7/8信号在老年小鼠的肺泡巨噬细胞中受损。在体内，老年小鼠感染呼吸道合胞病毒后IL-1β和骨桥蛋白的诱导较青年小鼠延迟，但延长。综上所述，这项研究证实了年轻和老年小鼠对RSV感染的反应存在内在差异，并伴随着抗病毒基因诱导和细胞因子信号转导的延迟。
Elderly persons are more susceptible to RSV-induced pneumonia than young people, but the molecular mechanism underlying this susceptibility is not well understood. In this study, we used an aged mouse model of RSV-induced pneumonia to examine how aging alters the lung pathology, modulates antiviral gene expressions, and the production of inflammatory cytokines in response to RSV infection. Young (2–3 months) and aged (19–21 months) mice were intranasally infected with mucogenic or non-mucogenic RSV strains, lung histology was examined, and gene expression was analyzed. Upon infection with mucogenic strains of RSV, leukocyte infiltration in the airways was elevated and prolonged in aged mice compared to young mice. Minitab factorial analysis identified several antiviral genes that are influenced by age, infection, and a combination of both factors. The expression of five antiviral genes, including pro-inflammatory cytokines IL-1β and osteopontin (OPN), was altered by both age and infection, while age was associated with the expression of 15 antiviral genes. Both kinetics and magnitude of antiviral gene expression were diminished as a result of older age. In addition to delays in cytokine signaling and pattern recognition receptor induction, we found TLR7/8 signaling to be impaired in alveolar macrophages in aged mice. In vivo, induction of IL-1β and OPN were delayed but prolonged in aged mice upon RSV infection compared to young. In conclusion, this study demonstrates inherent differences in response to RSV infection in young vs. aged mice, accompanied by delayed antiviral gene induction and cytokine signaling.
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影响因子：
3.6
作者：
Cabalka, AK
通讯作者：
Cabalka, AK
影响因子：
7.9
作者：
Cherukuri, Anu;Stokes, Kate L.;Lee, Sujin
通讯作者：
Lee, Sujin
影响因子：
5.5
作者：
Cyr, Sonya L.;Jones, Taff;Ward, Brian J.
通讯作者：
Ward, Brian J.
影响因子：
5.3
作者：
Boehmer, ED;Meehan, MJ;Kovacs, EJ
通讯作者：
Kovacs, EJ
影响因子：
--
作者：
Cherukuri, Anu;Patton, Kathryn;Tang, Roderick S.
通讯作者：
Tang, Roderick S.