Impaired immune responses in the lungs of aged mice following influenza infection.
Impaired immune responses in the lungs of aged mice following influenza infection.
复制标题
流感感染后，老年小鼠肺的免疫反应受损。
DOI：
10.1186/1465-9921-10-112
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发表时间：
2009-11-18
影响因子：
5.8
通讯作者：
Ross TM
中科院分区：
文献类型：
--
作者：
Toapanta FR;Ross TM
每年，流感病毒感染都会导致严重的发病率和死亡率，特别是在最易感的人群中，包括儿童、老年人（> 65岁）和慢性呼吸道疾病患者。导致老年人易感性增加的几个因素包括慢性病（如糖尿病）的发病率较高和免疫系统的衰老。在本研究中，用亚致死剂量的流感病毒感染老年和成年小鼠（A/波多黎各/8/1934）。分析了体重减轻、发病率、病毒滴度和先天性和适应性免疫应答细胞肺浸润动力学的差异。此外，还测定了这些细胞产生的主要细胞因子和趋化因子。与成年小鼠相比，老年小鼠的发病率更高，体重减轻更快，从感染中恢复更慢。与成年动物相比，老年小鼠肺中粒细胞和常规树突状细胞（cDC）的积累延迟，但巨噬细胞的积累没有延迟。老年动物中APC的延迟浸润动力学与其活化（CD40表达）的改变相关，这也与肺匀浆中细胞因子和趋化因子的延迟检测相关。这与自然杀伤（NK）、CD4+和CD8 + T细胞的延迟肺浸润有关。此外，与老年小鼠相比，成年小鼠中活化的（CD69+）流感特异性和IL-2产生性CD8 + T细胞的百分比更高。此外，成年B细胞的活化（CD69+）更早，并且与成年动物中中和抗体的更快发展相关。总体而言，APC引发和活化的改变导致肺中细胞因子和趋化因子的延迟产生，其最终影响流感感染后免疫细胞的浸润。这导致适应性免疫反应的延迟激活，随后延迟清除病毒，并延长老年动物的患病时间。由于老年人是发达国家人口中增长最快的部分，因此更好地了解衰老过程中免疫系统发生的变化是开发新疫苗和佐剂以改善该人群免疫应答的优先事项。
Each year, influenza virus infection causes severe morbidity and mortality, particularly in the most susceptible groups including children, the elderly (>65 years-old) and people with chronic respiratory diseases. Among the several factors that contribute to the increased susceptibility in elderly populations are the higher prevalence of chronic diseases (e.g. diabetes) and the senescence of the immune system. In this study, aged and adult mice were infected with sublethal doses of influenza virus (A/Puerto Rico/8/1934). Differences in weight loss, morbidity, virus titer and the kinetics of lung infiltration with cells of the innate and adaptive immune responses were analyzed. Additionally, the main cytokines and chemokines produced by these cells were also assayed. Compared to adult mice, aged mice had higher morbidity, lost weight more rapidly, and recovered more slowly from infection. There was a delay in the accumulation of granulocytic cells and conventional dendritic cells (cDCs), but not macrophages in the lungs of aged mice compared to adult animals. The delayed infiltration kinetics of APCs in aged animals correlated with alteration in their activation (CD40 expression), which also correlated with a delayed detection of cytokines and chemokines in lung homogenates. This was associated with retarded lung infiltration by natural killer (NK), CD4+ and CD8+ T-cells. Furthermore, the percentage of activated (CD69+) influenza-specific and IL-2 producer CD8+ T-cells was higher in adult mice compared to aged ones. Additionally, activation (CD69+) of adult B-cells was earlier and correlated with a quicker development of neutralizing antibodies in adult animals. Overall, alterations in APC priming and activation lead to delayed production of cytokines and chemokines in the lungs that ultimately affected the infiltration of immune cells following influenza infection. This resulted in delayed activation of the adaptive immune response and subsequent delay in clearance of virus and prolonged illness in aged animals. Since the elderly are the fastest growing segment of the population in developed countries, a better understanding of the changes that occur in the immune system during the aging process is a priority for the development of new vaccines and adjuvants to improve the immune responses in this population.
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影响因子：
3.7
作者：
Bright RA;Carter DM;Crevar CJ;Toapanta FR;Steckbeck JD;Cole KS;Kumar NM;Pushko P;Smith G;Tumpey TM;Ross TM
通讯作者：
Ross TM
影响因子：
15.9
作者：
Herrero, C;Marqués, L;Celada, A
通讯作者：
Celada, A
影响因子：
4.4
作者：
Hogan, RJ;Usherwood, EJ;Woodland, DL
通讯作者：
Woodland, DL
影响因子：
5.4
作者：
KIESSLING, R;KLEIN, E;WIGZELL, H
通讯作者：
WIGZELL, H
影响因子：
5.4
作者：
KIESSLING, R;KLEIN, E;WIGZELL, H
通讯作者：
WIGZELL, H