Dysregulation of key cytokines may contribute to increased susceptibility of diabetic mice to Mycobacterium bovis BCG infection

Alim, Md Abdul, Sikder, Suchandan, Sathkumara Mudiyanselage, Harindra, Kupz, Andreas, Rush, Catherine, Govan, Brenda, and Ketheesan, Natkunam (2019) Dysregulation of key cytokines may contribute to increased susceptibility of diabetic mice to Mycobacterium bovis BCG infection. Tuberculosis, 115. pp. 113-120.

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Abstract

Diabetes is one of the major co-morbidities contributing to the high global burden of tuberculosis (TB). The increased susceptibility of individuals with type 2 diabetes (T2D) to TB is multifactorial and may influence the efficacy of vaccines. This study was undertaken to determine the early immune responses that occur following infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG) in a diet-induced murine model of T2D. The phagocytic capabilities of alveolar (AM) and resident peritoneal macrophages (RPM) were assessed using ex vivo assays. Compared to macrophages from non-diabetic mice, macrophages from diabetic animals showed decreased BCG uptake and killing and inflammatory cytokine production (TNF-α, MCP-1, IL-6, IL-1β). In vivo susceptibility to BCG was determined following intravenous infection and diabetic mice showed a trend towards increased mortality, higher bacterial burden in the lung, liver and spleen and increased inflammatory lesions compared to controls. Differences between tissue cytokines were observed as early as one day post-infection and by days 14 and 35, lung and liver TNF-α and IFN-γ levels were decreased in diabetic mice compared to controls. These results suggest that early dysregulated immune responses may influence the susceptibility of T2D mice to BCG infection.

Item ID: 59102
Item Type: Article (Research - C1)
ISSN: 1873-281X
Keywords: Bacille Calmette-Guérin; murine model; macrophage; phagocytosis; type 2 diabetes; tuberculosis
Copyright Information: © 2019 Elsevier Ltd. All rights reserved.
Funders: James Cook University
Date Deposited: 02 Aug 2019 04:45
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 34%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060599 Microbiology not elsewhere classified @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110399 Clinical Sciences not elsewhere classified @ 33%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50%
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