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Title: Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria
Authors: Tan, K.S. 
Lee, K.O.
Low, K.C.
Gamage, A.M.
Liu, Y.
Tan, G.-Y.G.
Koh, H.Q.V.
Alonso, S.
Gan, Y.-H. 
Issue Date: 1-Jun-2012
Source: Tan, K.S., Lee, K.O., Low, K.C., Gamage, A.M., Liu, Y., Tan, G.-Y.G., Koh, H.Q.V., Alonso, S., Gan, Y.-H. (2012-06-01). Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria. Journal of Clinical Investigation 122 (6) : 2289-2300. ScholarBank@NUS Repository.
Abstract: Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12-IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast, IL-12 production in diabetic cells was not affected upon Salmonella enterica infection or in response to TLR2, -3, -4, and -5 ligands. Poor IL-12 production correlated with a deficiency in intracellular reduced glutathione (GSH) concentrations in diabetic patients. Addition of GSH or N-acetylcysteine to PBMCs selectively restored IL-12 and IFN-γ production and improved bacterial killing. Furthermore, the depletion of GSH in mice led to increased susceptibility to melioidosis, reduced production of IL-12p70, and poorer disease outcome. Our data thus establish a link between GSH deficiency in diabetes and increased susceptibility to melioidosis that may open up new therapeutic avenues to protect diabetic patients against some intracellular bacterial pathogens.
Source Title: Journal of Clinical Investigation
ISSN: 00219738
DOI: 10.1172/JCI57817
Appears in Collections:Staff Publications

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