Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, Whereas T- and B-cell-dependent immunity are less critical
Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, Whereas T- and B-cell-dependent immunity are less critical
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DOI：
10.1128/jvi.78.6.2701-2710.2004
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Harris, E
中科院分区：
文献类型：
--
作者：
Shresta, S;Kyle, JL;Harris, E
登革热病毒（DEN）引起登革热和登革出血热/登革休克综合征，这是世界范围内的主要公共卫生问题。控制DEN感染或导致严重疾病的免疫因素既不清楚，也不容易在人类中进行检查。在本研究中，我们使用缺乏多种免疫系统成分的野生型和基因型小鼠来研究DEN感染应答的免疫机制。我们的研究结果表明，α / β干扰素（ifn - α / β）和ifn - γ受体在解决原发性DEN感染方面具有关键的、不重叠的功能。此外，我们发现ifn - α / β受体介导的作用限制了DEN在神经外部位的初始复制，并控制随后病毒向中枢神经系统（CNS）的传播。相比之下，ifn - γ受体介导的应答似乎在DEN疾病的晚期通过限制病毒在外周的复制和从中枢神经系统消除病毒而起作用。缺乏B、CD4(+) T或CD8(+) T细胞的小鼠对DEN的易感性没有增加；然而，RAG小鼠（B细胞和T细胞均缺乏）对DEN感染部分易感。综上所述，(i) IFN- α / β对于DEN感染的早期免疫反应至关重要，（ii） IFN- γ介导的免疫反应对于小鼠DEN感染的早期和晚期清除至关重要，（iii） IFN系统在小鼠原发性DEN感染的抵抗中比T和b细胞依赖免疫发挥更重要的作用。
Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-alpha/beta) and IFN-gamma receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-alpha/beta receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-gamma receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4(+) T, or CD8(+) T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-alpha/beta is critical for early immune responses to DEN infection, (ii) IFN-gamma-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.