Reciprocal interactions between the intestinal microbiota and immunoglobulin A

肠道永久性地定植有密集而复杂的微生物群体，统称为微生物群。众所周知，微生物群的组分，如肠道细菌，诱导伊加型抗体。这些抗体反过来又结合肠道细菌并控制它们在宿主生物体中的生长和扩张。因此，伊加系统实质上有助于控制肠道中保护性免疫和耐受性之间的复杂平衡。该系统的紊乱可导致免疫病理学，如炎症性肠病和腹泻。在这个项目中，我们利用新的高通量测序技术来分析伊加系统和微生物群之间的相互关系。具体而言，我们的目标是：1）研究伊加系统对微生物群变化的适应性，例如抗生素治疗后。2）确定伊加抗体的微生物特异性和3）检查伊加系统对微生物群的影响。这些实验将有助于更好地了解免疫和耐受性之间的病理失衡如何发展并引发微生物群紊乱。此外，这些实验可能对口服疫苗的发展产生深远的影响。

The gut is permanently colonized with a dense and complex population of microorganisms, collectively known as microbiota. It is well know that components of the microbiota, such as commensal gut bacteria, induce IgA type antibodies. These antibodies in turn bind commensal bacteria and control their growth and expansion in the host organism. Thus the IgA system substantially contributes to control the intricate balance between protective immunity and tolerance in the gut. Disturbance of this system can result in immunopathologies such as inflammatory bowel disease and diarrhea. In this project we exploit newly available high-throughput sequencing technologies to analyse the interrelation between the IgA system and the microbiota. Specifically we aim at:1) Studying adaptation of the IgA system in response to changes in the microbiota, e.g. after antibiotic therapy.2) Determining the microbe-specificity of IgA antibodies and3) Examining the impact of the IgA system on the microbiota.These experiments will help to better understand how pathological misbalances between immunity and tolerance can develop and trigger disturbance of the microbiota. Moreover, these experiments might have profound effects on the development of oral vaccines.