Bacterial Quorum Sensing Molecules Promote Allergic Airway Inflammation by Activating the Retinoic Acid Response

Renlan Wu; Xingjie Li; Ning Ma; Xiufeng Jin; Xiefang Yuan; Chen Qu; Hongmei Tang; Zhigang Liu; Zongde Zhang

doi:10.1016/j.isci.2020.101288

Bacterial Quorum Sensing Molecules Promote Allergic Airway Inflammation by Activating the Retinoic Acid Response

iScience. 2020 Jul 24;23(7):101288. doi: 10.1016/j.isci.2020.101288. Epub 2020 Jun 20.

Authors

Renlan Wu¹, Xingjie Li², Ning Ma³, Xiufeng Jin³, Xiefang Yuan³, Chen Qu⁴, Hongmei Tang³, Zhigang Liu⁵, Zongde Zhang⁶

Affiliations

¹ Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Model Animal Research Center, Nanjing University, Nanjing 210061, China.
² Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China.
³ Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
⁴ Model Animal Research Center, Nanjing University, Nanjing 210061, China.
⁵ State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen 518060, China.
⁶ Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China; Model Animal Research Center, Nanjing University, Nanjing 210061, China. Electronic address: zongdez@swmu.edu.cn.

Abstract

IgE and IgG1 production in the type 2 immune response is the characteristic feature of an allergic reaction. However, whether bacterial molecules modulate IgE and IgG1 production remains obscure. Here, we demonstrate that the bacterial quorum sensing molecules acyl homoserine lactones (AHLs) induce IgE and IgG1 production by activating the RARE (retinoic acid response element) response in dendritic cells (DCs) in vivo. DC-specific knockout of the retinoic acid transcriptional factor Rara diminished the AHL-stimulated type 2 immune response in vitro. AHLs altered DC phenotype, upregulated OX40L and IFN-I signature, and promoted T helper 2 cell differentiation in vitro. Finally, AHLs activated the RARE response by inhibiting AKT phosphorylation in vitro, as the AKT agonists IGF-1 and PDGF abolished the effect of AHLs on the RARE response. This study demonstrates a mechanism by which AHLs drive allergic airway inflammation through activating retinoic acid signaling in DCs.

Keywords: Biological Sciences; Immune Response; Immunology.