Transport of antibody into the skin is only partially dependent upon the neonatal Fc-receptor.
Transport of antibody into the skin is only partially dependent upon the neonatal Fc-receptor.
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DOI：
10.1371/journal.pone.0273960
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
真皮是大多数媒介传播的病原体进入的门户，因此宿主在这个部位的免疫反应对于减轻感染的程度至关重要。对于疟疾，最近证明了抗体介导的真皮中和疟原虫。然而，令人惊讶的是，人们对支配抗体进入皮肤的机制知之甚少。由于新生儿Fc受体(FcRN)被证实能将细胞内的免疫球蛋白(Ig G)转运到不同的组织中，我们试图了解其在蚊虫叮咬接种后对皮肤中的Ig G转运以及抗体介导的抑制疟原虫感染的作用。利用共聚焦成像技术，我们发现，在缺乏FcRN的小鼠中，抗兰格林单抗进入皮肤的转运发生了，但只有部分减少。为了了解FcRN在疟疾感染背景下的相关性，我们使用啮齿寄生虫伯氏疟原虫，并表明在FcRN缺陷小鼠中被动注射抗疟疾抗体并不能像以前在野生型小鼠中观察到的那样减少寄生虫负担。总体而言，我们的数据表明，FcRN在将免疫球蛋白运送到皮肤中起作用，但不是将免疫球蛋白运送到该组织的主要驱动力。这些发现对合理设计以抗体为基础的疟疾和其他媒介传播病原体的治疗方法具有重要意义。
The dermis is the portal of entry for most vector-transmitted pathogens, making the host’s immune response at this site critical in mitigating the magnitude of infection. For malaria, antibody-mediated neutralization of Plasmodium parasites in the dermis was recently demonstrated. However, surprisingly little is known about the mechanisms that govern antibody transport into the skin. Since the neonatal Fc receptor (FcRn) has been shown to transcytose IgG into various tissues, we sought to understand its contribution to IgG transport into the skin and antibody-mediated inhibition of Plasmodium parasites following mosquito bite inoculation. Using confocal imaging, we show that the transport of an anti-Langerin mAb into the skin occurs but is only partially reduced in mice lacking FcRn. To understand the relevance of FcRn in the context of malaria infection, we use the rodent parasite Plasmodium berghei and show that passively-administered anti-malarial antibody in FcRn deficient mice, does not reduce parasite burden to the same extent as previously observed in wildtype mice. Overall, our data suggest that FcRn plays a role in the transport of IgG into the skin but is not the major driver of IgG transport into this tissue. These findings have implications for the rational design of antibody-based therapeutics for malaria as well as other vector-transmitted pathogens.
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影响因子：
30.5
作者：
Merad, M;Manz, MG;Engleman, EG
通讯作者：
Engleman, EG
DOI：
10.1073/pnas.0810796106
发表时间：
2009-02-24
影响因子：
11.1
作者：
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通讯作者：
Ward, E. Sally
影响因子：
3.1
作者：
Medica, DL;Sinnis, P
通讯作者：
Sinnis, P
影响因子：
4.4
作者：
Ober, RJ;Martinez, C;Ward, ES
通讯作者：
Ward, ES
DOI：
10.1084/jem.20101488
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coppi A;Natarajan R;Pradel G;Bennett BL;James ER;Roggero MA;Corradin G;Persson C;Tewari R;Sinnis P
通讯作者：
Sinnis P