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

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…

• NN
  National Natural Science Foundation of China

  Awards: 2042022dx0003, U22A20335
• SA
  Science and Technology Department of Hubei Province
• NK
  National Key Research and Development Program of China

  Awards: 2023YFC2307800, 2021YFC2701800
• FR
  Fundamental Research Funds for the Central Universities

  Award: 2042022dx0003