Increased susceptibility to Mycobacterium tuberculosis infection in a diet-induced murine model of type 2 diabetes |
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| Institution: | 1. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia;2. Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh;3. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns & Townsville, Queensland, Australia;4. College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia;5. University of New England, New South Wales, Australia;1. Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, 480-1195, Japan;2. Department of Molecular Biology and Chemistry, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan;3. Department of Anatomy, Mongolian National University of Medical Sciences, Ulaanbaatar, 210648, Mongolia;1. Department of Public Health and Pediatric Sciences, University of Turin, Medical School, Turin, Italy;2. Department of Pediatrics, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy;1. Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of São Paulo, São Paulo, Brazil;2. Division of Clinical Dermatology, Medical School, University of São Paulo, São Paulo, Brazil;3. Tropical Medicine Institute, University of São Paulo, São Paulo, Brazil;1. Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil;2. Department of Physics, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil;3. School of Medical Sciences, Universidade Federal de Mato Grosso, Cuiabá, MT, 78060-900, Brazil |
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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 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. |
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| Keywords: | Macrophage Murine model Type 2 diabetes-tuberculosis co-morbidity |
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