Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Epalinges, Switzerland.
Nat Immunol. 2021 Mar;22(3):279-286. doi: 10.1038/s41590-020-00856-3. Epub 2021 Jan 25.
The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody-microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize L-tyrosine. This model led to increased concentrations of p-cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe-derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma.
肠道微生物群的组成取决于局部栖息地，而栖息地本身又受到免疫压力的影响，如黏膜 IgA。使用一种抗体库受限的小鼠模型，我们发现抗体-微生物相互作用在塑造具有增强代谢 L-酪氨酸能力的细菌群落方面发挥了作用。该模型导致了 p- 对甲酚硫酸盐（PCS）浓度的增加，这使宿主能够对抗过敏性气道炎症。PCS 通过解耦表皮生长因子受体（EGFR）和 Toll 样受体 4（TLR4）信号，选择性地减少气道上皮细胞 CCL20 的产生。总之，这些数据揭示了一种源自肠道微生物的代谢产物途径，它可以在气道上皮细胞的远端发挥作用，从而减少过敏性气道反应，如哮喘的基础反应。
