Microbial metabolism of L-tyrosine protects against allergic airway inflammation

Tomasz P Wypych; Céline Pattaroni; Olaf Perdijk; Carmen Yap; Aurélien Trompette; Dovile Anderson; Darren J Creek; Nicola L Harris; Benjamin J Marsland

doi:10.1038/s41590-020-00856-3

Microbial metabolism of L-tyrosine protects against allergic airway inflammation

Nat Immunol. 2021 Mar;22(3):279-286. doi: 10.1038/s41590-020-00856-3. Epub 2021 Jan 25.

Authors

Tomasz P Wypych¹, Céline Pattaroni², Olaf Perdijk², Carmen Yap², Aurélien Trompette³, Dovile Anderson⁴, Darren J Creek⁴, Nicola L Harris², Benjamin J Marsland⁵

Affiliations

¹ Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia. [email protected].
² Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
³ Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Epalinges, Switzerland.
⁴ Monash Proteomics and Metabolomics Facility, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
⁵ Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia. [email protected].

PMID: 33495652
DOI: 10.1038/s41590-020-00856-3

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Allergens
Animals
Antibodies / immunology
Antibodies / metabolism*
Antibody Diversity
Bacteria / immunology
Bacteria / metabolism*
Cells, Cultured
Chemokine CCL20 / metabolism
Coculture Techniques
Cresols / administration & dosage
Cresols / metabolism*
Disease Models, Animal
ErbB Receptors / metabolism
Female
Gastrointestinal Microbiome*
Host-Pathogen Interactions
Injections, Intravenous
Intestines / microbiology*
Lung / immunology
Lung / metabolism*
Lung / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pneumonia / immunology
Pneumonia / metabolism
Pneumonia / microbiology
Pneumonia / prevention & control*
Respiratory Hypersensitivity / immunology
Respiratory Hypersensitivity / metabolism
Respiratory Hypersensitivity / microbiology
Respiratory Hypersensitivity / prevention & control*
Signal Transduction
Sulfuric Acid Esters / administration & dosage
Sulfuric Acid Esters / metabolism*
Toll-Like Receptor 4 / metabolism
Tyrosine / administration & dosage
Tyrosine / metabolism*

Substances

Allergens
Antibodies
CCL20 protein, mouse
Chemokine CCL20
Cresols
Sulfuric Acid Esters
Tlr4 protein, mouse
Toll-Like Receptor 4
Tyrosine
4-cresol sulfate
EGFR protein, mouse
ErbB Receptors