Mechanisms of commensal bacteria induced humoral immunity

微生物群影响人类健康的许多方面，并与疾病有关，如 肥胖、炎症性肠病、糖尿病和过敏，宿主和共生体之间的平衡 细菌在大多数健康的人身上都保存得很好。对肠道有贡献的一个宿主因素 动态平衡是免疫球蛋白亚类的抗体。在粘膜中发现了产生免疫球蛋白的浆细胞！组织，如 作为肠道的固有层，但也可以在包括骨髓在内的全身部位发现。 然而，只有在某些细菌联合存在的情况下，才能发现高水平的骨髓LGA。 骨髓分泌LGA的浆细胞的频率增加与浓度的增加有关 在多菌传播的脓毒症模型中，已被证明具有保护作用的血清免疫球蛋白。这个 细菌诱导全身性LGA反应的机制尚不清楚。这项提议的主要目标是 采取公正的方法来定义共生细菌用来诱导 此外，我们还将研究物种间的相互作用如何影响系统性LGA的特异性。 总之，这项建议将提供一个框架，以了解系统性抗体反应是如何 对共生细菌的反应而诱导的。这一理解可能会导致旨在 维持肠道内环境稳定或使用共生细菌作为疫苗输送系统。这项建议 将支持我们研究计划的总体愿景，以了解 细菌和宿主通过破译细菌在基因水平上使用的机制来诱导LGA反应。

The microbiome affects many aspects of human health and has been linked to diseases such as obesity, inflammatory bowel disease, diabetes, and allergy, The balance between host and commensal bacteria is well maintained in most healthy individuals. One host factor that contributes to intestinal homeostasis is antibody of the lgA subclass. Plasma cells that produce lgA are found in mucosa! tissues such as the lamina propria of the gut, but they can also be found in systemic sites including the bone marrow. However, high levels of bone marrow lgA are only found in the presence of certain consortia of bacteria. Increased frequencies of bone marrow lgA-secreting plasma cells are associated with increased concentration of serum lgA that has been shown to be protective in a sepsis model of polymicrobial dissemination. The mechanisms by which bacteria induce systemic lgA responses are unknown. The main goal of this proposal is to take an unbiased approach to defining gene-level mechanisms used by commensal bacteria to induce systemic lgA Additionally, we will examine how inter-species interactions contribute to systemic lgA specificity. Together, this proposal will provide a framework for understanding how systemic antibody responses are induced in response to commensal bacteria. This understanding could lead to novel therapies aimed at maintaining intestinal homeostasis or using commensal bacteria as a vaccine delivery system. This proposal will support the overall vision of our research program to understand the complex interplay at the interface of bacteria and host by deciphering gene-level mechanisms used by bacteria to induce lgA responses.