4.6 Article

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

期刊

MICROBES AND INFECTION
卷 22, 期 8, 页码 303-311

出版社

ELSEVIER
DOI: 10.1016/j.micinf.2020.03.004

关键词

Mycobacterium tuberculosis; Macrophage; Murine model; Type 2 diabetes-tuberculosis co-morbidity

资金

  1. Endeavour postgraduate Scholarship (PhD) from the Australian Government, Department of Education and Training, Australia
  2. National Health and Medical Research Council, Australia [APP1140709]

向作者/读者索取更多资源

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. (C) 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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