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Abstract

(Mtb) kills more people than any other infectious agent worldwide. Our group has shown the importance of glycolysis in controlling intracellular Mtb growth in human macrophages1, which leads to increased lactate production. Therefore, we examined if lactate had an immunomodulatory effect on human monocyte derived macrophages (hMDM) infected with Mtb.

hMDM were adherence purified from healthy donor buffy coats with human serum for 6-8 days. Sodium L-Lactate was added 3 hours prior to infection with Mtb or stimulation with LPS (100 ng/ml). Macrophage phenotype and function was assessed by ELISA, flow cytometry and Seahorse metabolic-flux analysis. Bacillary killing was determined by colony forming units (CFU) after lysing infected hMDM, plating on middlebrook agar and counting 21 days later.

25 mM of lactate improves hMDM ability to control intracellular Mtb growth with a 55% reduction in CFU at day 5 post infection. The glycolytic response seen immediately following infection with Mtb or LPS stimulation was decreased with lactate. LPS-induced upregulation of activation markers was diminished by lactate.

Lactate is a product of aerobic glycolysis induced by infection and supports the intracellular killing of Mtb. Further research is required to elucidate the mechanism of this effect.

1. Gleeson, L. E. Cutting Edge: Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication. 196, 2444–2449 (2016).

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/content/journal/acmi/10.1099/acmi.mim2019.po0025
2020-01-01
2020-02-28
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.mim2019.po0025
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