Interkingdom Communication and Regulation of Mucosal Immunity by the Microbiome

Intercellular communication and environmental sensing are most often mediated through ligand-receptor binding and signaling. This is true for both host cells and microbial cells. The ligands can be proteins (cytokines, growth factors, and peptides), modified lipids, nucleic acid derivatives and small molecules generated from metabolic pathways. These latter nonprotein metabolites play a much greater role in the overall function of mucosal immunity than previously recognized, and the list of potential immunomodulatory molecules derived from the microbiome is growing. The most well-studied microbial signals are the nonmetabolite microbe-associated molecular pattern molecules, such as lipopolysaccharide and teichoic acid, that bind to host pattern recognition receptors. Here, we will highlight the immunomodulatory activities of other microbiome-derived molecules, such as short-chain fatty acids, bile acids, uric acid, prostaglandins, histamine, catecholamines, aryl hydrocarbon receptor ligands, and 12,13-diHOME.