TY - JOUR
T1 - Emerging role of D-Amino acid metabolism in the innate defense
AU - Sasabe, Jumpei
AU - Suzuki, Masataka
N1 - Funding Information:
We thank M. Yasui for indispensable support. JS was funded by JSPS KAKENHI Grant Number 16K09327, Moritani Scholarship Foundation, and Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research. MS was supported by JSPS KAKENHI Grant Number 18K07181 and Grant-in-Aid for JSPS Research Fellow (Grant Number 17J10213).
Publisher Copyright:
© 2018 Sasabe and Suzuki.
PY - 2018/5/9
Y1 - 2018/5/9
N2 - Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals. At host-microbe interfaces in the neutrophils and intestinal mucosa, DAO catalyzes oxidation of bacterial D-amino acids, such as D-alanine, and generates H2O2, which is linked to antimicrobial activity. Intestinal DAO also modifies the composition of microbiota through modulation of growth for some bacteria that are dependent on host nutrition. Furthermore, regulation and recognition of D-amino acids in mammals have additional meanings at various host-microbe interfaces; D-phenylalanine and D-tryptophan regulate chemotaxis of neutrophils through a G-coupled protein receptor, D-serine has a bacteriostatic role in the urinary tract, D-phenylalanine and D-leucine inhibit innate immunity through the sweet taste receptor in the upper airway, and D-tryptophan modulates immune tolerance in the lower airway. This mini-review highlights recent evidence supporting the hypothesis that D-amino acids are utilized as inter-kingdom communication at host-microbe interface to modulate bacterial colonization and host defense.
AB - Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals. At host-microbe interfaces in the neutrophils and intestinal mucosa, DAO catalyzes oxidation of bacterial D-amino acids, such as D-alanine, and generates H2O2, which is linked to antimicrobial activity. Intestinal DAO also modifies the composition of microbiota through modulation of growth for some bacteria that are dependent on host nutrition. Furthermore, regulation and recognition of D-amino acids in mammals have additional meanings at various host-microbe interfaces; D-phenylalanine and D-tryptophan regulate chemotaxis of neutrophils through a G-coupled protein receptor, D-serine has a bacteriostatic role in the urinary tract, D-phenylalanine and D-leucine inhibit innate immunity through the sweet taste receptor in the upper airway, and D-tryptophan modulates immune tolerance in the lower airway. This mini-review highlights recent evidence supporting the hypothesis that D-amino acids are utilized as inter-kingdom communication at host-microbe interface to modulate bacterial colonization and host defense.
KW - D-amino acid
KW - D-amino acid oxidase
KW - Host-microbe interaction
KW - Hydrogen peroxide
KW - Innate immunity
KW - Mucosal immunity
KW - Neutrophil
KW - Small intestine
UR - http://www.scopus.com/inward/record.url?scp=85046995858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046995858&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2018.00933
DO - 10.3389/fmicb.2018.00933
M3 - Short survey
AN - SCOPUS:85046995858
VL - 9
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
IS - MAY
M1 - 933
ER -