[ODP-173] Analysis of host immunity through HIF-1 activating factor Mint3 in Listeria monocytogenes infection
Introduction: Mint3/Apba3 regulates glycolysis-dependent energy production via activation of HIF-1, a hypoxia-responsive transcription factor, in macrophages. Mint3-deficient mice have been reported to be resistant to endotoxin shock, but their contribution to the immune response against pathogenic bacteria remains unclear. In this study, we focused on the function of Mint3 and aimed to elucidate the role of Mint3-mediated host response mechanisms in the infection of Listeria monocytogenes (LM).
Methods: Mint3-deficient mice were intraperitoneally infected with LM and we compared their survival rate and the bacterial burden in their organs with wild-type (WT) mice. We also compared intracellular bacterial burden, ROS and NO production, caspase-1 activation in macrophages infected with LM.
Results: Our results showed that Mint3-deficient mice were more resistant to lethal listeriosis than WT mice. Additionally, ablation of Mint3 markedly increased the activation of caspase-1, maturation of gasdermin D, and pyroptosis in macrophages infected with LM in vitro. Further analyses revealed that Mint3 depletion upregulates inflammasome assembly preceding pyroptosis via glycolysis reduction and reactive oxygen species production.
Discussion: Our results suggest that Mint3 depletion promotes pyroptosis in host macrophages, thereby preventing the spread of LM infection.