RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.
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DOI：
10.1016/j.cell.2018.08.064
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发表时间：
2018-10-04
期刊：
影响因子：
64.5
通讯作者：
Haynes BF
中科院分区：
文献类型：
--
作者：
Bradley T;Peppa D;Pedroza-Pacheco I;Li D;Cain DW;Henao R;Venkat V;Hora B;Chen Y;Vandergrift NA;Overman RG;Edwards RW;Woods CW;Tomaras GD;Ferrari G;Ginsburg GS;Connors M;Cohen MS;Moody MA;Borrow P;Haynes BF
HIV-1广泛中和抗体（bnAb）很难用疫苗诱导，但在大约50%的HIV-1感染者中产生。了解宿主控制bnAb诱导的分子机制对疫苗设计至关重要。在这里，我们对47名HIV-1感染者的血液单核细胞进行了转录组分析，这些HIV-1感染者制造了bnAb，46名HIV-1感染者没有制造bnAb，并在bnAb个体中鉴定了RAB 11 FIP 5的上调，RAB 11 FIP 5编码与再循环内体相关的Rab效应蛋白。自然杀伤（NK）细胞的RAB 11 FIP 5的差异表达最高，这与bnAb受试者中NK细胞亚群的更大失调有关。来自bnAb个体的NK细胞具有更多的适应性/功能失调表型，并表现出与RAB 11 FIP 5转录水平相关的脱粒和细胞因子产生受损。此外，RAB 11 FIP 5过表达调节NK细胞的功能。这些数据表明，NK细胞和Rab 11再循环内体转运参与调节HIV-1 bnAb的发展。RAB 11 FIP 5表达升高与HIV-1 bnAb诱导相关NK细胞显示最高差异RAB 11 FIP 5表达NK细胞亚群在发展bnAb的个体中更失调Rab 11 Fip 5调节NK细胞功能人类中针对HIV-1的广泛中和抗体的产生与自然杀伤细胞中特异性再循环内体相关效应物的表达相关。
HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induction is critical to vaccine design. Here, we performed a transcriptome analysis of blood mononuclear cells from 47 HIV-1-infected individuals who made bnAbs and 46 HIV-1-infected individuals who did not and identified in bnAb individuals upregulation of RAB11FIP5, encoding a Rab effector protein associated with recycling endosomes. Natural killer (NK) cells had the highest differential expression of RAB11FIP5, which was associated with greater dysregulation of NK cell subsets in bnAb subjects. NK cells from bnAb individuals had a more adaptive/dysfunctional phenotype and exhibited impaired degranulation and cytokine production that correlated with RAB11FIP5 transcript levels. Moreover, RAB11FIP5 overexpression modulated the function of NK cells. These data suggest that NK cells and Rab11 recycling endosomal transport are involved in regulation of HIV-1 bnAb development. Elevated RAB11FIP5 expression is associated with HIV-1 bnAb induction NK cells show the highest differential RAB11FIP5 expression NK cell subsets are more dysregulated in individuals developing bnAbs Rab11Fip5 regulates NK cell function Generation of broadly neutralizing antibodies against HIV-1 in humans is linked to the expression of a specific recycling endosome-associated effector in natural killer cells.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Davies, R.;Hammenfors, D.;Appel, S.
通讯作者：
Appel, S.
影响因子：
6.4
作者：
Guma, Monica;Cabrera, Cecilia;Lopez-Botet, Miguel
通讯作者：
Lopez-Botet, Miguel
影响因子：
5.5
作者：
Cook, Kevin D.;Kline, Hannah C.;Whitmire, Jason K.
通讯作者：
Whitmire, Jason K.