Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection
Diet-Induced Obesity Impairs the T Cell Memory Response to Influenza Virus Infection
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DOI：
10.4049/jimmunol.0903220
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发表时间：
2010-03-15
影响因子：
4.4
通讯作者：
Beck, Melinda A.
中科院分区：
文献类型：
--
作者：
Karisson, Erik A.;Sheridan, Patricia A.;Beck, Melinda A.
美国疾病控制与预防中心表示，肥胖可能是 H1N1 流感大流行毒株导致疾病严重程度增加的一个独立危险因素。原发性流感感染期间产生的记忆 T 细胞以流感病毒常见的内部蛋白为目标，使其能够有效抵御异源毒株的侵袭。在饮食诱导肥胖的雄性 C57BL/6 小鼠中，原发性 H3N2 感染后的继发性 H1N1 流感攻击导致死亡率 25%（瘦对照没有损失）、肺部病理学增加 25%、体重无法恢复以及肺部病毒滴度升高 10 至 100 倍。此外，与瘦对照小鼠相比，肥胖小鼠肺部的 IFN-γ mRNA 表达量减少了 60% 以上，二次感染后产生 IFN-γ 的流感特异性 CD8+ T 细胞数量也减少了三分之一。当用来自瘦小鼠的流感脉冲树突状细胞刺激时，来自肥胖小鼠的记忆CD8(+) T细胞的IFN-γ产生减少>50%。因此，流感特异性记忆T细胞的功能在肥胖小鼠的肺部显着降低且无效。全球肥胖流行的现实加上每年流感爆发和当前的大流行，使得了解流感病毒感染在肥胖宿主中的不同表现至关重要。此外，记忆反应受损对肥胖人群的疫苗功效具有重大影响。免疫学杂志，2010，184：3127-3133。
The Centers for Disease Control and Prevention has suggested that obesity may be an independent risk factor for increased severity of illness from the H1N1 pandemic strain. Memory T cells generated during primary influenza infection target internal proteins common among influenza viruses, making them effective against encounters with heterologous strains. In male, diet-induced obese C57BL/6 mice, a secondary H1N1 influenza challenge following a primary H3N2 infection led to a 25% mortality rate (with no loss of lean controls), 25% increase in lung pathology, failure to regain weight, and 10- to 100-fold higher lung viral titers. Furthermore, mRNA expression for IFN-gamma was >60% less in lungs of obese mice, along with one third the number of influenza-specific CD8(+) T cells producing IFN-gamma postsecondary infection versus lean controls. Memory CD8(+) T cells from obese mice had a >50% reduction in IFN-gamma production when stimulated with influenza-pulsed dendritic cells from lean mice. Thus, the function of influenza-specific memory T cells is significantly reduced and ineffective in lungs of obese mice. The reality of a worldwide obesity epidemic combined with yearly influenza outbreaks and the current pandemic makes it imperative to understand how influenza virus infection behaves differently in an obese host. Moreover, impairment of memory responses has significant implications for vaccine efficacy in an obese population. The Journal of Immunology, 2010, 184: 3127-3133.