Impact of IgG Isotype on the Induction of Antibody-Dependent Cellular Phagocytosis of HIV by Human Milk Leukocytes.
Impact of IgG Isotype on the Induction of Antibody-Dependent Cellular Phagocytosis of HIV by Human Milk Leukocytes.
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DOI：
10.3389/fimmu.2022.831767
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
每年约有100 000例通过母乳喂养的艾滋病毒母婴传播事件。然而，由未经治疗的HIV阳性母亲喂养的婴儿中只有约15%被感染，这表明牛奶本身具有保护作用。婴儿每天通过乳汁摄入105-108个母体白细胞，这些白细胞在摄入后仍保持功能。这种功能可以由母乳抗体（Ab）引起。虽然伊加在牛奶中占主导地位，但大多数HIV特异性牛奶抗体都属于IgG亚类，这突出了研究牛奶中每个IgG同种型功能的重要性。尽管由恒定（Fc）结构域通过与Fc受体（FcR）相互作用介导的Ab效应子功能（例如Ab依赖性细胞吞噬作用（ADCP））在保护免受HIV感染中是关键的，但ADCP在很大程度上未被探索，因为它涉及MTCT的减轻。目前，我们报告了ADCP活性的牛奶白细胞对艾滋病毒颗粒和免疫复合物（IC），使用57个独特的样品从34名妇女，引起IgG 1/2/3/4的单克隆抗体（m）246-D。当由IgG 1/3/4引起时，HIV的粒细胞ADCP与其他吞噬细胞相比是最有效的。IgG 1/3类似地激活粒细胞，与IgG 2/4相比，表现出1.6倍-4.4倍的活性，并且与IC相比，对病毒具有偏好。值得注意的是，给定靶标的CD 16-单核细胞ADCP不受同种型的影响，并且CD 16+单核细胞受IgG 1的刺激很差。IgG 2/4引起有效的IC ADCP，并且就总白细胞IC ADCP而言，IgG 4和IgG 3表现出相似的功能，与IgG 1/IgG 2相比，IgG 4引起1.6倍-2.1倍的活性，并且CD 16+单核细胞最受IgG 2刺激。这些数据有助于更全面地了解Fc介导的乳汁白细胞功能，这对于开发消除这种MTCT途径的治疗方法至关重要，包括粘膜给予mAb和/或母体接种，旨在引起有效的乳汁Ab应答。
Approximately 100,000 mother-to-child transmission (MTCT) events of HIV via human milk feeding occur each year. However, only about 15% of infants milk-fed by untreated HIV+ mothers become infected, suggesting a protective effect of the milk itself. Infants ingest 105-108 maternal leukocytes daily via milk, which remain functional beyond ingestion. Such function may be elicited by maternal milk antibody (Ab). Though IgA is dominant in milk, most HIV-specific milk Abs are of the IgG subclass, highlighting the importance of investigating the function of each IgG isotype in the milk context. Though Ab effector function mediated by the constant (Fc) domain via interaction with Fc Receptors (FcRs), such as Ab-dependent cellular phagocytosis (ADCP), are critical in protecting against HIV infection, ADCP is largely unexplored as it relates to mitigation of MTCT. Presently we report the ADCP activity of milk leukocytes against HIV particles and immune complexes (ICs), using 57 unique samples from 34 women, elicited by IgG1/2/3/4 of monoclonal (m)Ab 246-D. Granulocyte ADCP of HIV was most potent compared to other phagocytes when elicited by IgG1/3/4. IgG1/3 activated granulocytes similarly, exhibiting 1.6x-4.4x greater activity compared to IgG2/4, and a preference for virus compared to ICs. Notably, CD16- monocyte ADCP of a given target were unaffected by isotype, and CD16+ monocytes were poorly stimulated by IgG1. IgG2/4 elicited potent IC ADCP, and in terms of total leukocyte IC ADCP, IgG4 and IgG3 exhibited similar function, with IgG4 eliciting 1.6x-2.1x greater activity compared to IgG1/IgG2, and CD16+ monocytes most stimulated by IgG2. These data contribute to a more comprehensive understanding of Fc-mediated functionality of milk leukocytes, which is critical in order to develop therapeutic approaches to eliminating this route of MTCT, including mucosal administration of mAbs and/or a maternal vaccination aimed to elicit a potent milk Ab response.
从人初乳中分离出 HIV-1 中和粘膜单克隆抗体。
影响因子：
3.7
作者：
Friedman J;Alam SM;Shen X;Xia SM;Stewart S;Anasti K;Pollara J;Fouda GG;Yang G;Kelsoe G;Ferrari G;Tomaras GD;Haynes BF;Liao HX;Moody MA;Permar SR
通讯作者：
Permar SR