Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes.

Autor: Martinez N; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA., Smulan LJ; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA., Jameson ML; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA., Smith CM; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA., Cavallo K; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA., Bellerose M; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA., Williams J; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA., West K; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA., Sassetti CM; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA., Singhal A; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.; A*STAR Infectious Diseases Labs (ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, 138648, Singapore.; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, 138648, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore., Kornfeld H; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA. Hardy.Kornfeld@umassmed.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 20; Vol. 14 (1), pp. 5840. Date of Electronic Publication: 2023 Sep 20.
DOI: 10.1038/s41467-023-41519-9
Abstrakt: Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that male mice receiving a high-fat diet and streptozotocin to model type 2 diabetes, have higher mortality, more lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. Type 2 diabetes model mice have elevated plasma glycerol, which is a preferred carbon source for M. tuberculosis. Infection studies with glycerol kinase mutant M. tuberculosis reveal that glycerol utilization contributes to the susceptibility of the type 2 diabetes mice. Hyperglycemia impairs protective immunity against M. tuberculosis in both forms of diabetes, but our data show that elevated glycerol contributes to an additional adverse effect uniquely relevant to type 2 diabetes.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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