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. (In Press)

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Abstract

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 suscep- tibility 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.
Date Deposited: 13 Aug 2020 05:48
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 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%
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