Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation.

ABSTRACT: Trained immunity refers to the long-term memory of the innate immune cells. However, little is known about how environmental nutrient availability influences trained immunity. This study finds that physiologic carbon sources impact glucose contribution to the tricarboxylic acid (TCA) cycle and enhance cytokine production of trained monocytes. Our experiments demonstrate that trained monocytes preferentially employe lactate over glucose as a TCA cycle substrate, and lactate metabolism is required for trained immune cell responses to bacterial and fungal infection. Except for the contribution to the TCA cycle, endogenous lactate or exogenous lactate also supports trained immunity by regulating histone lactylation. Further transcriptome analysis, ATAC-seq, and CUT&Tag-seq demonstrate that lac

SUBMITTER: Cai H 

PROVIDER: S-EPMC11971257 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature