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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective
Frontiers in Cellular and Infection Microbiology, Volume 11, Article 691823, Year 2021
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Description
Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerance vs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection with M. tuberculosis (Mtb) H37Rv after the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-α, IFN-γ, IFN-β and IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association. © Copyright © 2021 Sinha, Ngo, Bartlett, Bielefeldt-Ohmann, Keshvari, Hasnain, Donovan, Kling, Blumenthal, Chen, Short and Ronacher.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8291147/bin/Table_1.docx
Authors & Co-Authors
Sinha, Roma
Australia, Woolloongabba
Translational Research Institute Australia
Ngo, Minh Dao
Australia, Woolloongabba
Translational Research Institute Australia
Bartlett, Stacey
Australia, Woolloongabba
Translational Research Institute Australia
Bielefeldt-Ohmann, Helle
Australia, Brisbane
The University of Queensland
Australia, Brisbane
Australian Infectious Diseases Research Centre
Blumenthal, Antje
Australia, Brisbane
Australian Infectious Diseases Research Centre
Australia, Brisbane
The University of Queensland
Ronacher, Katharina
Australia, Woolloongabba
Translational Research Institute Australia
Australia, Brisbane
Australian Infectious Diseases Research Centre
Statistics
Citations: 8
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.3389/fcimb.2021.691823
ISSN:
22352988
Research Areas
Infectious Diseases
Noncommunicable Diseases
Study Approach
Quantitative