biostudies-literatureMa LMinistry of Science and Technology of the People’s Republic of ChinaStrategic Priority Research Program of the Chinese Academy of SciencesNational Natural Science Foundation of China1385-1400https://www.ebi.ac.uk/biostudies/studies/S-EPMC9225223biostudies-literatureUnknown18(6)Macrophages rapidly undergo glycolytic reprogramming in response to macroautophagy/autophagy, inflammasome activation and pyroptosis for the clearance of bacteria. Identification the key molecules involved in these three events will provide critical potential therapeutic applications. Upon <i>S. typhimurium</i> infection, FLT4/VEGFR3 and its ligand VEGFC were inducibly expressed in macrophages, and FLT4 signaling inhibited CASP1 (caspase 1)-dependent inflammasome activation and pyroptosis but enhanced MAP1LC3/LC3 activation for elimination of the bacteria. Consistently, FLT4 mutants lacking the extracellular ligand-binding domain increased production of the proinflammatory metabolites such as succinate and lactate, and reduced antimicrobial metabolites including citrate and NAD(P)H in macrAutophagyFLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.PMC92252232016YFC09059022016YFC09059002016YFD0500407819300382016YFD05002072018YFA080070230671038816300438180157581671572817015693170078181825011XDB190000008196116073881571552Qi LMa LWei BLu YZhang LWang HYu HLi NLi WHe YZhang YZhao QZhou FWu YfalseFLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.Macrophages rapidly undergo glycolytic reprogramming in response to macroautophagy/autophagy, inflammasome activation and pyroptosis for the clearance of bacteria. Identification the key molecules involved in these three events will provide critical potential therapeutic applications. Upon <i>S. typhimurium</i> infection, FLT4/VEGFR3 and its ligand VEGFC were inducibly expressed in macrophages, and FLT4 signaling inhibited CASP1 (caspase 1)-dependent inflammasome activation and pyroptosis but enhanced MAP1LC3/LC3 activation for elimination of the bacteria. Consistently, FLT4 mutants lacking the extracellular ligand-binding domain increased production of the proinflammatory metabolites such as succinate and lactate, and reduced antimicrobial metabolites including citrate and NAD(P)H in macr2022-01-01T00:00:00Z2022 Jun2025-04-22T08:00:26.201Z2025-04-05T22:20:43.037ZS-EPMC92252233463291810.1080/15548627.2021.1985338