Altered macrophage function is associated with severe Burkholderia pseudomallei infection in a murine model of type 2 diabetes.

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.

journal_name

Microbes Infect

journal_title

Microbes and infection

authors

Hodgson KA,Morris JL,Feterl ML,Govan BL,Ketheesan N

doi

10.1016/j.micinf.2011.07.008

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1177-84

issue

14-15

eissn

1286-4579

issn

1769-714X

pii

S1286-4579(11)00195-X

journal_volume

13

pub_type

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