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Nat Microbiol:流感下幸存的肺细胞“不一般”

2019-07-31 佚名 生物通

杜克大学的科学家们鉴定出一种名为棒状细胞(club cell)的肺细胞,它们能在流感A病毒攻击下存活下来,并迅速修复受损的DNA,而周围的其他细胞则成片死亡。

杜克大学的科学家们鉴定出一种名为棒状细胞(club cell)的肺细胞,它们能在流感A病毒攻击下存活下来,并迅速修复受损的DNA,而周围的其他细胞则成片死亡。



杜克医学院分子遗传学和微生物学助理教授Nicholas Heaton说,棒状细胞存在于肺泡上方最狭窄的气道中。这些细胞的正常功能是生产表面活性剂并分泌覆盖肺部衬里的各种其他蛋白质。

Heaton团队在2014年发现棒状细胞可以在能杀死大部分细胞的流感感染中存活下来。在2016年的一项研究中,他们观察到病毒攻击下的棒状细胞启动了蛋白质制造机制并向免疫系统发出信号,产生高水平的促炎分子(细胞因子)。

Heaton说,棒状细胞的存活让肺部在感染被清除后仍对新病毒有一定的敌意。

作为证据,他指出,2009年夏天爆发流感大流行(不是常见的秋季或冬季流感),巧合的是那年的另一种基于RNA的季节性病毒,呼吸道合胞病毒(RSV),却无法感染人群,似乎人群对它能够更好地做出抵抗。

“这表明,流感让人们的身体发生了变化,使人更好地抵抗另一种呼吸道感染,”Heaton说。“棒状细胞很可能就是起作用的份子。”

“我们从以前的研究中晓得,棒状细胞可以活,但是我们却不知道它们是怎么活下来的,”Heaton说。

7月29日新发表的《Nature Microbiology》杂志报道了Heaton实验室与宾夕法尼亚大学Sara Cherry等人对感染过程中棒状细胞抗病毒反应的新见解。他们发现这些细胞面对感染,加大了DNA错配的修复力度。

活性氧是入侵病毒的武器,会破坏宿主细胞内任何开放和活跃的DNA片段。通常情况下,损伤积累到细胞无法表达抵抗病毒所需的基因的程度,细胞就会死亡。

但是棒状细胞会加倍努力地修复DNA损伤,从而幸存下来。为了证实这一点,研究人员构建了一种携带可以击溃人类棒状细胞中所有DNA修复机制的工程病毒,结果棒状细胞像其他呼吸细胞一样死于这种流感。

在体内幸存下来的棒状细胞继续生产表面活性剂和化学物质以促进炎症。“如果此时一种病毒进入,它面临的是一个非常抗病毒的环境,”Heaton说。这可以解释2009年没有如期而至的RSV流行。

“现在我们知道感染造成大量细胞过度发炎,”Heaton说。“如果我们耗尽棒状细胞,炎症就会减少,这提示了治疗慢性阻塞性肺疾病或哮喘的一个重要线索。”

现在,杜克大学已经提交了一份将DNA错配修复作为实验室培养流感疫苗菌株的方法的临时专利申请。

原始出处:Benjamin S. Chambers, Brook E. Heaton, Keiko Rausch, et al. DNA mismatch repair is required for the host innate response and controls cellular fate after influenza virus infection. Nat Microbiol. 29 July 2019

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    2019-09-20 sunylz
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    2019-09-15 xjy02
  5. [GetPortalCommentsPageByObjectIdResponse(id=1663441, encodeId=6bf11663441ee, content=<a href='/topic/show?id=c8f982280c2' target=_blank style='color:#2F92EE;'>#肺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82280, encryptionId=c8f982280c2, topicName=肺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=765025615163, createdName=thinkibmz_44722602, createdTime=Mon Jan 13 12:07:00 CST 2020, time=2020-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767681, encodeId=a6ba1e67681d1, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Fri Mar 20 05:07:00 CST 2020, time=2020-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918792, encodeId=79a71918e92da, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Sep 20 05:07:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084544, encodeId=6ce22084544f2, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sun Sep 15 23:07:00 CST 2019, time=2019-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883813, encodeId=3fd618838130d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Mar 06 18:07:00 CST 2020, time=2020-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857823, encodeId=3397185e823e6, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Apr 01 04:07:00 CST 2020, time=2020-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370639, encodeId=26753e0639a4, content=谢谢了,学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30331616752, createdName=txqjm, createdTime=Fri Aug 02 07:12:57 CST 2019, time=2019-08-02, status=1, ipAttribution=)]
    2020-03-06 liye789132251
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    2019-08-02 txqjm

    谢谢了,学习

    0

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