Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia 
pseudomallei. Type 2 diabetes (T2D) is the most common comorbidity associated 
with melioidosis. B. pseudomallei isolates from melioidosis patients with T2D 
are less virulent in animal models than those from patients with melioidosis and 
no identifiable risk factors. We developed an ex vivo whole-blood assay as a 
tool for comparison of early inflammatory profiles generated by T2D and 
nondiabetic (ND) individuals in response to a B. pseudomallei strain of low 
virulence. Peripheral blood from individuals with T2D, with either poorly 
controlled glycemia (PC-T2D [n = 6]) or well-controlled glycemia (WC-T2D [n = 
8]), and healthy ND (n = 13) individuals was stimulated with B. pseudomallei. 
Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen 
recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and 
HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. 
Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, 
tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], 
IL-8, IL-1β, and IL-10) were also determined. Following stimulation, oxidative 
burst and MPO levels were significantly elevated in blood from PC-T2D subjects 
compared to controls. Differences were also observed in expression of Toll-like 
receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. 
Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from 
PC-T2D subjects compared to ND individuals. Notably, differential inflammatory 
responses of PC-T2D, WC-T2D, and ND individuals to B. pseudomallei occur 
independently of bacterial load and confirm the efficacy of this model of 
T2D-melioidosis comorbidity as a tool for investigation of dysregulated PMN and 
monocyte responses to B. pseudomallei underlying susceptibility of T2D 
individuals to melioidosis.