Supplementary Material for: <b><i>Slc6a13</i></b> Deficiency Attenuates <b><i>Pasteurella multocida</i></b> Infection-Induced Inflammation via Glycine-Inflammasome Signaling

We have previously demonstrated that Slc6a13-deficient (Slc6a13^−/−; KO) mice are resistant to <i>P</i>. <i>multocida</i> infection, which might be in connection with macrophage-mediated inflammation; however, the specific metabolic mechanism is still enigmatic. Here we reproduce the less sensitive to <i>P</i>. <i>multocida</i> infection in overall survival assays as well as reduced bacterial loads, tissue lesions, and inflammation of lungs in KO mice. The transcriptome sequencing analysis of wild-type (WT) and KO mice shows a large number of differentially expressed genes that are enriched in amino acid metabolism by functional analysis. Of note, glycine levels are substantially increased in the lungs of KO mice with or without <i>P</i>. <i>multocida</i> infection in comparison to the WT controls. Interestingly, exogenous glycine supplementation alleviates <i>P</i>. <i>multocida</i> infection-induced inflammation. Mechanistically, glycine reduces the production of inflammatory cytokines in macrophages by blocking the activation of inflammasome (NALP1, NLRP3, NLRC4, AIM2, and Caspase-1). Together, Slc6a13 deficiency attenuates <i>P</i>. <i>multocida</i> infection through lessening the excessive inflammatory responses of macrophages involving glycine-inflammasome signaling.