Microbial metabolism of L-tyrosine protects against allergic airway inflammation.
Tomasz Piotr WypychCéline PattaroniOlaf PerdijkCarmen YapAurélien TrompetteDovile AndersonDarren J CreekNicola L HarrisBenjamin J MarslandPublished in: Nature immunology (2021)
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.
Keyphrases
- toll like receptor
- epidermal growth factor receptor
- allergic rhinitis
- tyrosine kinase
- inflammatory response
- nuclear factor
- advanced non small cell lung cancer
- mouse model
- immune response
- climate change
- small cell lung cancer
- chronic obstructive pulmonary disease
- mental health
- microbial community
- healthcare
- genome wide
- nitric oxide
- lung function
- nitric oxide synthase
- single cell
- air pollution
- machine learning
- data analysis