Gupta Suman, Gupta Sneh Lata, Singh Aashima, Oswal Neelam, Bal Vineeta, Rath Satyajit, George Anna, Basu Srijani
Mucosa Immunology Laboratory, National Institute of Immunology, New Delhi, India.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Crohns Colitis 360. 2023 May 26;5(3):otad030. doi: 10.1093/crocol/otad030. eCollection 2023 Jul.
Classically, IgA in the gut prevents the invasion of microorganisms to systemic organs through the process of neutralization and immune exclusion. Interestingly, recent reports suggest that IgA might help in biofilm formation and promote bacterial growth inside the intestine.
In this study, we used flow cytometry, ELISA, and chemical models of colitis to test whether the quality and quantity of IgA can select for bacterial persistence in the gut.
We found that members of Proteobacteria, such as γ-Proteobacteria and SFB, are preferentially coated by IgA in WT mice. In the partial absence of either T-dependent or -independent IgA responses, there are no significant differences in the frequency of bacteria coated with IgA in mice. However, Rag-/- mice that lack all antibodies had a severe reduction in Proteobacteria and were resistant to DSS-induced colitis, suggesting that secretory IgA might be essential for differential retention of these taxa in the mouse gut. Rag-/- littermates in the F2 generation generated from (B6 × Rag-/-) F1 mice acquired the underrepresented bacteria taxa such as γ-Proteobacteria through vertical transmission of flora. They died soon after weaning, possibly due to the acquired flora. Additionally, continued exposure of Rag-/- mice to B6 flora by cohousing mice led to the acquisition of γ-Proteobacteria and mortality.
Together, our results indicate that host survival in the complete absence of an IgA response necessitates the exclusion of specific bacterial taxa from the gut microbiome.
传统上，肠道中的IgA通过中和和免疫排斥过程防止微生物侵入全身器官。有趣的是，最近的报道表明IgA可能有助于生物膜形成并促进肠道内细菌生长。
在本研究中，我们使用流式细胞术、酶联免疫吸附测定和结肠炎化学模型来测试IgA的质量和数量是否能选择肠道中的细菌持久性。
我们发现，在野生型小鼠中，变形菌门成员，如γ-变形菌和梭状芽孢杆菌属细菌优先被IgA包被。在部分缺乏T细胞依赖性或非依赖性IgA反应的情况下，小鼠中被IgA包被的细菌频率没有显著差异。然而，缺乏所有抗体的Rag-/-小鼠中变形菌门细菌数量严重减少，并对右旋糖酐硫酸钠诱导的结肠炎具有抗性，这表明分泌型IgA可能是这些分类群在小鼠肠道中差异保留所必需的。由（B6×Rag-/-）F1小鼠产生的F2代中的Rag-/-同窝小鼠通过菌群的垂直传播获得了代表性不足的细菌分类群，如γ-变形菌。它们在断奶后不久死亡，可能是由于获得的菌群。此外，通过将Rag-/-小鼠与B6小鼠合笼饲养，使其持续暴露于B6菌群中，导致其获得γ-变形菌并死亡。
总之，我们的结果表明，在完全没有IgA反应的情况下，宿主的生存需要从肠道微生物群中排除特定的细菌分类群。
