Increased susceptibility to Mycobacterium tuberculosis infection in a diet-induced murine model of type 2 diabetes

Alim, Mohammad Abdul, Kupz, Andreas, Sikder, Suchandan, Rush, Catherine, Govan, Brenda, and Ketheesan, Natkunam (2020) Increased susceptibility to Mycobacterium tuberculosis infection in a diet-induced murine model of type 2 diabetes. Microbes and Infection, 22 (8). pp. 303-311.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website:


Tuberculosis (TB)-type 2 diabetes mellitus (T2D) comorbidity is re-emerging as a global public health problem. T2D is a major risk factor for increased susceptibility to TB infection and reactivation leading to higher morbidity and mortality. The pathophysiological mechanisms of T2D contributing to TB susceptibility are not fully understood, but likely involve dysregulated immune responses. In this study, a diet-induced murine model that reflects the cardinal features of human T2D was used to assess the immune responses following an intravenous Mycobacterium tuberculosis (Mtb) infection. In this study, T2D significantly increased mortality, organ bacillary burden and inflammatory lesions compared to non-diabetic controls. Organ-specific pro-inflammatory cytokine responses were dysregulated as early as one day post-infection in T2D mice. Macrophages derived from T2D mice showed reduced bacterial internalization and killing capacity. An early impairment of antimycobacterial functions of macrophages in diabetes is a key mechanism that leads to increased susceptibility of T2D.

Item ID: 64077
Item Type: Article (Research - C1)
ISSN: 1769-714X
Keywords: Mycobacterium tuberculosis; MacrophageMurine model; Type 2 diabetes-tuberculosis co-morbidity
Copyright Information: © 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC APP1140709
Date Deposited: 13 Aug 2020 05:48
FoR Codes: 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320211 Infectious diseases @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320407 Innate immunity @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 65%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 35%
Downloads: Total: 4
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page