Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults
Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults
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DOI：
10.1093/infdis/jiu573
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发表时间：
2015-04-01
影响因子：
6.4
通讯作者：
Shaw, Albert C.
中科院分区：
文献类型：
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作者：
Mohanty, Subhasis;Joshi, Samit R.;Shaw, Albert C.
我们评估了67名年轻人（年龄21-30岁）和老年人（年龄>= 65岁）在流感疫苗接种前后单核细胞群的体内先天免疫应答。接种后，年轻人和老年人均诱导产生了CD 14（+）CD 16（+）炎性单核细胞。在经典的CD 14（+）CD 16（-）和炎性单核细胞中，通过细胞内染色测量，接种后强烈诱导肿瘤坏死因子a和白细胞介素6的产生。细胞因子的产生与流感疫苗抗体应答密切相关;在年轻受试者中，最高水平出现在接种疫苗后第28天，而在老年受试者中则大幅降低。值得注意的是，在接种疫苗之前和之后，来自老年受试者的单核细胞中的抗炎细胞因子白细胞介素10（IL-10）的水平显著升高。在纯化的单核细胞中，我们发现与年龄相关的磷酸化信号转导子和转录激活子-3升高，并减少了负IL-10调节剂双特异性磷酸酶1的丝氨酸359磷酸化。这些发现首次表明，在老年人中，IL-10的产生失调与疫苗应答受损有关。
We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged >= 65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor a and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults.