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

Journal Publication ResearchOnline@JCU
Alim, Mohammad Abdul;Kupz, Andreas;Sikder, Suchandan;Rush, Catherine;Govan, Brenda;Ketheesan, Natkunam
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 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.

Journal

Microbes and Infection

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Volume

22

ISBN/ISSN

1769-714X

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Issue

8

Pages Count

9

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Publisher

Elsevier

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N/A

DOI

10.1016/j.micinf.2020.03.004