导读 | 一种终生携带的、曾被科学家们认为会削弱免疫系统的病毒竟能让老年小鼠更“强壮”。这是美国科学家在近日发表的一篇PNAS论文中获得的惊人发现。 |
图片来源:PNAS
为了寻找一种使老年人的免疫系统恢复活力的方法,美国亚利桑那大学Janko Nikolich-Zugich博士带领的研究小组意外地发现,一种原本被认为会削弱免疫系统的特殊病毒实际上发挥着“增强免疫系统”的作用。相关成果于7月2日以“Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection”为题发表在PNAS杂志上。
具体来说,在这项研究中,科学家们用巨细胞病毒(cytomegalovirus,CMV)感染了小鼠。事实上,该病毒影响了超过一半的个体,其中,大部分在年轻的时候就被感染了。由于无法治愈,因此CMV通常被终生携带,在老年人中尤为普遍。
论文第一作者Megan J. Smithey博士说:“CMV通常不会引起外在症状,但我们不得不每天与它‘共同生活’。我们的免疫系统总是忙于对付这种病毒。”
那么,这种“终生病毒”(lifelong virus)最终是如何影响免疫系统的呢?Smithey博士等猜测,CMV会使小鼠更容易受到其他感染的攻击,因为它耗尽了资源,一直使免疫系统处于忙碌的状态。
然而,事实并非如科学家们所猜测的那样。
研究发现,当感染李斯特菌时,携带CMV的老年小鼠会比未携带CMV的老年小鼠会更强壮。
“这一结果让我们非常惊讶。我们原以为,携带CMV的小鼠情况会更糟,但它们对感染却有更强大、有效的反应。”Smithey博士说。
图片来源:16sucai
尽管目前研究者们还不清楚CMV是如何增强免疫系统的,但他们正在一项独立的研究中调查这一问题。在该研究中,他们对衰老免疫系统有了新的认识。
多年来,免疫生物学家一直认为,T细胞(抵抗感染的防卫军)的多样性会随着年龄的增长而减少。这就是为什么老年人更容易死于疾病的原因之一。然而,Smithey博士和Nikolich-Zugic博士却发现,年老小鼠的T细胞与年轻小鼠的T细胞一样具有多样性。不过,在老年小鼠中,多种多样的T细胞并不会被招募到“战场上”,除非小鼠感染了CMV。
Nikolich-Zugic博士说:“不同类型的T细胞可对不同类型的感染做出反应。你拥有的T细胞越多样化,你就越有可能抵抗感染。”
“我们的新研究表明,在老年时,个体具有产生良好免疫反应的能力,而CMV或机体对CMV的反应能够帮助利用这种能力。”Smithey博士补充道。
据悉,Nikolich-Zugic博士等将继续研究CMV。他们希望在人类研究中看到类似的结果。该小组的最终目标是,开发出一种能够改善老年人免疫系统,帮助预防感染的疫苗。
责编:风铃
参考资料:
This virus actually may boost—not weaken—our immune system
Lifelong interactions between host and the ubiquitous and persistent cytomegalovirus (CMV) have been proposed to contribute to the age-related decline in immunity. Prior work from us and others found some support for that idea, yet evidence that this led to increased vulnerability to other infections was not obtained. Moreover, evidence has accumulated that CMV infection can be beneficial to immune defense in young/adult mice and humans, dominantly via enhanced innate immunity. Here, we describe an unexpected impact of murine CMV (MCMV) upon the T cell response of old mice to Listeria monocytogenes expressing the model antigen, OVA (Lm-OVA). Single-cell sequencing of the OVA-specific CD8 T cell receptor β (TCRβ) repertoire of old mice demonstrated that old MCMV-infected mice recruited many diverse clonotypes that afforded broad and often more efficient recognition of antigenic peptide variants. This stood in contrast to old control mice, which exhibited strong narrowing and homogenization of the elicited repertoire. High-throughput sequencing of the total naïve CD8 TCRβ repertoire showed that many of these diverse OVA-specific clonotypes were present in the naïve CD8 repertoire of mice in all groups (adult, old control, and old MCMV+) yet were only recruited into the Lm-OVA response in MCMV+ old mice. These results have profound implications for our understanding of T cell immunity over a life span and suggest that our coevolution with CMV may include surprising, potentially positive impacts on adaptive heterologous immunity in late life.
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