PMID- 22473609
OWN - NLM
STAT- MEDLINE
DCOM- 20120717
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 80
IP  - 6
DP  - 2012 Jun
TI  - Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood 
      model of type 2 diabetes-melioidosis comorbidity.
PG  - 2089-99
LID - 10.1128/IAI.00212-12 [doi]
AB  - 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-alpha], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1beta, 
      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.
FAU - Morris, Jodie
AU  - Morris J
AD  - Infectious Diseases and Immunopathogenesis Research Group, Discipline of 
      Microbiology and Immunology, James Cook University, Townsville, Queensland, 
      Australia. Jodie.Morris1@jcu.edu.au
FAU - Williams, Natasha
AU  - Williams N
FAU - Rush, Catherine
AU  - Rush C
FAU - Govan, Brenda
AU  - Govan B
FAU - Sangla, Kunwarjit
AU  - Sangla K
FAU - Norton, Robert
AU  - Norton R
FAU - Ketheesan, Natkunam
AU  - Ketheesan N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120402
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biological Assay/methods
MH  - Biomarkers/blood
MH  - Blood Glucose/analysis
MH  - Burkholderia pseudomallei/*physiology
MH  - Case-Control Studies
MH  - Comorbidity
MH  - Diabetes Mellitus, Type 2/*blood/epidemiology/metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/metabolism/*microbiology
MH  - Lymphocyte Activation
MH  - Male
MH  - Melioidosis/*blood/epidemiology/metabolism
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Neutrophils/metabolism
MH  - Respiratory Burst
PMC - PMC3370601
EDAT- 2012/04/05 06:00
MHDA- 2012/07/18 06:00
PMCR- 2012/12/01
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2012/07/18 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - IAI.00212-12 [pii]
AID - 00212-12 [pii]
AID - 10.1128/IAI.00212-12 [doi]
PST - ppublish
SO  - Infect Immun. 2012 Jun;80(6):2089-99. doi: 10.1128/IAI.00212-12. Epub 2012 Apr 2.