A Cardiolipin from Muribaculum intestinale Induces Antigen-Specific Cytokine Responses

• DOI: 10.1021/jacs.3c09734
• Publication Date: 2023-10-23T18:35:16Z
• Authors: Sunghee Bang; Yern-Hyerk Shin; Xiao Ma; Sung-Moo Park; Daniel B. Graham; Ramnik J. Xavier; Jon Clardy
• Keywords: Mammals; Mice; Toll-Like Receptor 6; Cardiolipins; Bacteroidetes; Animals; Cytokines

An systematic phenotypic screen of the mouse gut microbiome for metabolites with an immunomodulatory effect identified Muribaculum intestinale as one only two members oversized on T-cell populations. Here we report identification and characterization a lipid, MiCL-1, responsible metabolite. MiCL-1 is 18:1-16:0 cardiolipin, whose close relatives are found concave lipid surfaces both mammals bacteria. was synthesized to confirm structural analysis functionally characterized in cell-based assays. It has highly restrictive structure–activity profile, its chain-switched analog fails induce responses any our robustly induces production pro-inflammatory cytokines like TNF-α, IL-6, IL-23, but no detectable anti-inflammatory cytokine IL-10. As case other recently discovered lipids, requires functional TLR2 TLR1 not TLR6