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 M., Govan, Brenda L., 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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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: 58295
Item Type: Article (Research - C1)
ISSN: 1873-281X
Keywords: Bacille Calmette-Guérin, Murine model, Macrophage, Phagocytosis, Type 2 diabetes, Tuberculosis
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A version of this publication was included as Appendix 2 of the following PhD thesis: Sathkumara, Harindra Darshana (2020) Mechanisms driving tuberculosis susceptibility and vaccine efficacy in HIV/AIDS and type 2 diabetes. PhD thesis, James Cook University, which is available Open Access in ResearchOnline@JCU. Please see the Related URLs for access.

Date Deposited: 18 Oct 2019 02:09
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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