The zinc transporter Slc30a1 (ZnT1) in macrophages plays a protective role against attenuated .

The zinc transporter Slc30a1 plays an essential role in maintaining cellular zinc homeostasis. Despite this, its functional role in macrophages remains largely unknown. Here, we examine the function of Slc30a1 in host defense using mice models infected with an attenuated stain of Typhimurium and primary macrophages infected with the attenuated . Bulk transcriptome sequencing in primary macrophages identifies Slc30a1 as a candidate in response to infection. Whole-mount immunofluorescence and confocal microscopy imaging of primary macrophage and spleen from -infected mice demonstrate Slc30a1 expression is increased in infected macrophages with localization at the plasma membrane and in the cytosol. -Cre-driven conditional knockout mice () exhibit increased susceptibility to infection compared to control littermates. We demonstrate that Slc30a1-deficient macrophages are defective in intracellular killing, which correlated with reduced activation of nuclear factor kappa B and reduction in nitric oxide (NO) production. Notably, the model exhibits intracellular zinc accumulation, demonstrating that Slc30a1 is required for zinc export. We thus conclude that zinc export enables the efficient NO-mediated antibacterial activity of macrophages to control invading .