Microbial ecology perturbation in human IgA deficiency
Microbial ecology perturbation in human IgA deficiency
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DOI：
10.1126/scitranslmed.aan1217
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发表时间：
2018-05-02
影响因子：
17.1
通讯作者：
Gorochov, Guy
中科院分区：
文献类型：
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作者：
Fadlallah, Jehane;El Kafsi, Hela;Gorochov, Guy
矛盾的是，免疫球蛋白A(IgA)的丧失并不是不可挽回地导致人类严重感染，而是与相对轻微的呼吸道感染、特应性和自身免疫有关。因此，免疫球蛋白也可能扮演隐蔽的角色，而不是唯一与病原体控制有关的角色。我们表明，人类免疫球蛋白A缺乏与肠道微生物生态的大规模数量扰动无关。元基因组分析强调了预期的致病碱基扩张，但在一些典型有益的共生体中，预期的耗竭较少。通常存在于口咽部的物种的肠道定植也让人联想到空间微生物区系的混乱。免疫球蛋白只能部分挽救IgA缺乏症，因为并不是所有典型的IgA靶标都能有效地与肠腔中的IgM结合。综上所述，IgA似乎在免疫/微生物界面的前沿发挥着非多余的作用，远离肠道屏障，从病原体控制和全身炎症的调节到保护共生多样性和社区网络。
Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.