title: Impact of streptozotocin-induced diabetes on functional responses of dendritic cells and macrophages towards Burkholderia pseudomallei.
abstract: Diabetes mellitus is a documented risk factor for melioidosis, a tropical infection caused by Burkholderia pseudomallei. The increased susceptibility of diabetic individuals to infections with other pathogens has been associated with immune dysregulation. However, the impact of diabetes on the functional responses of dendritic cells (DC) and macrophages during B. pseudomallei infection has not been investigated. This study compared the responses of macrophages and DC towards B. pseudomallei using bone marrow-derived DC (BMDC) and peritoneal elicited macrophages (PEM) isolated from streptozotocin-induced diabetic C57BL/6 mice exhibiting hyperglycaemia for 9 days (acute) or 70 days (chronic) and age-matched nondiabetic C57BL/6 mice. Following coincubation of BMDC and PEM with a highly virulent B. pseudomallei isolate, maturation, bacterial internalization plus intracellular survival and cytokine gene expression profiles were assessed. No significant differences in functional responses of BMDC or PEM isolated from acute diabetic and nondiabetic mice were observed. However, significant differences in BMDC and PEM function were observed when chronic diabetic and nondiabetic mice were compared. This study demonstrates that diabetic mice with extended periods of uncontrolled hyperglycaemia have impaired DC and macrophage function towards B. pseudomallei, which may contribute to the high susceptibility observed in clinical practice.
authors.affiliation: School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Qld, Australia. natasha.williams@jcu.edu.au
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Williams
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Morris
authors.forename: Catherine
authors.initials: C
authors.lastname: Rush
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Govan
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
mesh_terms: D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000276:immunology*; D020869:Gene Expression Profiling; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D013311:Streptozocin / Q000633:toxicity*
chemical_list: D016207:Cytokines; D013311:Streptozocin