Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota
Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota
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DOI：
10.1073/pnas.1412984112
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发表时间：
2015-01-13
影响因子：
11.1
通讯作者：
Vernick, Kenneth D.
中科院分区：
文献类型：
--
作者：
Carissimo, Guillaume;Pondeville, Emilie;Vernick, Kenneth D.
虫媒病毒通过蚊子和其他节肢动物传播给人类和动物。与这些病毒相关的风险在全球范围内不断增加，包括欧洲和美洲的新出现。按蚊是人类疟疾的媒介，但据信传播一种已知的虫媒病毒，即奥-尼翁病毒，而伊蚊传播多种病毒。人们对按蚊与病毒的相互作用研究甚少，中肠中最初的抗病毒反应也尚未得到研究。在这里，我们确定的抗病毒免疫途径的冈比亚按蚊中肠，病毒感染后的感染性血餐的初始网站。我们将它们与后中肠系统性隔室的反应进行比较，后中肠系统性隔室是随后传播的病毒感染的部位。中肠的正常病毒感染需要细菌植物群，并且受到免疫缺陷（Imd）、JAK/STAT和富含Leu的重复免疫因子的活性的抑制。我们发现，外源性siRNA途径，被认为是典型的蚊子抗病毒途径，在中肠的抗病毒防御中没有可检测到的作用，但只在系统隔室中起保护作用。这些结果改变了流行的抗病毒范例，通过描述不同的身体隔室和感染阶段的不同保护机制。重要的是，中肠细菌植物群的存在是对按蚊的完全病毒感染性所必需的，与疟疾感染相反，疟疾感染需要中肠细菌植物群的存在来保护免受感染。因此，肠道植物群控制着载体对不同人类病原体的抗性的相互保护权衡。
Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o'nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens.