Critical role of CD4(+) T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection.
Critical role of CD4(+) T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection.
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DOI：
10.1038/s41467-018-05519-4
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发表时间：
2018-08-07
影响因子：
16.6
通讯作者：
Bozza MT
中科院分区：
文献类型：
--
作者：
Lucas CGO;Kitoko JZ;Ferreira FM;Suzart VG;Papa MP;Coelho SVA;Cavazzoni CB;Paula-Neto HA;Olsen PC;Iwasaki A;Pereira RM;Pimentel-Coelho PM;Vale AM;de Arruda LB;Bozza MT
寨卡病毒（ZIKV）的保护性适应性免疫主要归因于细胞毒性CD8 + T细胞和中和抗体，而CD4 + T细胞在抵抗中的作用在很大程度上尚未明确。在此，我们展示了一种中和抗体反应，它依赖于CD4 + T细胞和干扰素γ（IFNγ）信号传导，我们在感染的第一周检测到这种反应，并且它与大脑中病毒载量的降低、疾病快速发作的预防以及存活相关。我们证明了这些成分在原发性感染期间以及在干扰素受体（IFNR）缺陷背景下的异源寨卡病毒感染的小鼠过继转移模型中对寨卡病毒的抵抗中所起的作用。过继转移的CD4 + T细胞的保护作用在受体小鼠中需要IFNγ信号传导、CD8 + T细胞和B淋巴细胞。总之，这表明了CD4 + T细胞反应在未来寨卡病毒疫苗设计中的重要性。
对寨卡病毒保护性免疫的特征描述在很大程度上集中于CD8 + T细胞和抗体介导的保护。在此，作者展示了CD4 + T细胞以及相关的IFNγ信号传导在抗体介导的对寨卡病毒感染的抵抗中所起的作用。
Protective adaptive immunity to Zika virus (ZIKV) has been mainly attributed to cytotoxic CD8+ T cells and neutralizing antibodies, while the participation of CD4+ T cells in resistance has remained largely uncharacterized. Here, we show a neutralizing antibody response, dependent on CD4+ T cells and IFNγ signaling, which we detected during the first week of infection and is associated with reduced viral load in the brain, prevention of rapid disease onset and survival. We demonstrate participation of these components in the resistance to ZIKV during primary infection and in murine adoptive transfer models of heterologous ZIKV infection in a background of IFNR deficiency. The protective effect of adoptively transferred CD4+ T cells requires IFNγ signaling, CD8+ T cells and B lymphocytes in recipient mice. Together, this indicates the importance of CD4+ T cell responses in future vaccine design for ZIKV. Characterization of protective immunity to Zika virus has largely focussed on CD8+ T cells and antibody-mediated protection. Here the authors show roles for CD4+ T cells and the associated IFNγ signaling in antibody-mediated resistance to Zika virus infection.
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影响因子：
3.8
作者：
Dowall SD;Graham VA;Rayner E;Hunter L;Atkinson B;Pearson G;Dennis M;Hewson R
通讯作者：
Hewson R
影响因子：
64.8
作者：
Iijima N;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
11.8
作者：
Foy BD;Kobylinski KC;Chilson Foy JL;Blitvich BJ;Travassos da Rosa A;Haddow AD;Lanciotti RS;Tesh RB
通讯作者：
Tesh RB
影响因子：
3.8
作者：
Aliota MT;Dudley DM;Newman CM;Mohr EL;Gellerup DD;Breitbach ME;Buechler CR;Rasheed MN;Mohns MS;Weiler AM;Barry GL;Weisgrau KL;Eudailey JA;Rakasz EG;Vosler LJ;Post J;Capuano S 3rd;Golos TG;Permar SR;Osorio JE;Friedrich TC;O'Connor SL;O'Connor DH
通讯作者：
O'Connor DH
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K