title: 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.
authors.affiliation: Microbiology and Immunology, School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hodgson
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Morris
authors.forename: Marshall L
authors.initials: ML
authors.lastname: Feterl
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Govan
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000472:pathogenicity; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000276:immunology* / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology*; D008554:Melioidosis / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D016897:Respiratory Burst; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D001786:Blood Glucose; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha