Altered macrophage function is associated with severe Burkholderia pseudomallei infection in a murine model of type 2 diabetes
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Updated: May 30, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Kelly A Hodgson1, Jodie L Morris, Marshall L Feterl
1Microbiology and Immunology, School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811, Australia.
Abstract:
This study used a murine model of type 2 diabetes (BKS.Cg-Dock7(m) +/+Lepr(db)/J mice) to investigate the inflammatory and cellular mechanisms predisposing to Burkholderia pseudomallei infection and co-morbid diabetes. Homozygous db/db (diabetic) mice developed extreme obesity, dyslipidaemia and glucose intolerance leading to hyperglycaemia and overt type 2 diabetes. Compared to their heterozygous db/+ (non-diabetic) littermates, diabetic mice rapidly succumbed to subcutaneous B. pseudomallei infection, paralleled by severe hypoglycaemia and increased expression of the proinflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β, in the spleen, despite comparable bacterial loads in the spleen of non-diabetic mice. Neutrophil oxidative burst and dendritic cell uptake and killing of B. pseudomallei were similar between diabetic and non-diabetic mice. Compared to peritoneal macrophages from non-diabetic mice, macrophages from diabetic mice were unable to contain and kill B. pseudomallei. Functional differences between macrophages of diabetic and non-diabetic mice toward B. pseudomallei may contribute to rapid dissemination and more severe disease progression in hosts with co-morbid type 2 diabetes.
Insights
Type 2 diabetes impairs macrophage function, increasing susceptibility to Burkholderia pseudomallei infection. Diabetic mice showed severe disease and mortality due to impaired immune response.
Area of Science:
- Immunology
- Infectious Diseases
- Metabolic Disorders
Background:
- Type 2 diabetes is a global health concern.
- Burkholderia pseudomallei causes melioidosis, a serious infectious disease.
- Comorbidities like diabetes can exacerbate infectious disease outcomes.
Purpose of the Study:
- To investigate the impact of type 2 diabetes on susceptibility to Burkholderia pseudomallei infection.
- To elucidate the inflammatory and cellular mechanisms involved in this interaction.
- To understand how diabetes influences the host-pathogen interaction.
Main Methods:
- Utilized a murine model of type 2 diabetes (BKS.Cg-Dock7(m) +/+Lepr(db)/J mice).
- Compared diabetic (db/db) and non-diabetic (db/+) littermates following subcutaneous B. pseudomallei infection.
- Assessed inflammatory cytokine expression (TNF-α, IL-1β), bacterial loads, neutrophil function, dendritic cell activity, and peritoneal macrophage killing capacity.
Main Results:
- Diabetic mice exhibited severe obesity, dyslipidemia, hyperglycemia, and rapid mortality after infection.
- Increased pro-inflammatory cytokine expression (TNF-α, IL-1β) in the spleen of diabetic mice.
- Macrophages from diabetic mice showed impaired ability to contain and kill B. pseudomallei, unlike neutrophils and dendritic cells.
Conclusions:
- Impaired macrophage function in type 2 diabetes contributes to increased susceptibility and severe disease progression in Burkholderia pseudomallei infections.
- These findings highlight the critical role of macrophage dysfunction in comorbid diabetes and infectious disease.
- Understanding these mechanisms is crucial for developing targeted therapies for infected diabetic patients.
