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Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood model of type 2 diabetes-melioidosis comorbidity.
Infect Immun. 2012 Jun; 80(6):2089-99.II

Abstract

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.

Authors+Show Affiliations

Infectious Diseases and Immunopathogenesis Research Group, Discipline of Microbiology and Immunology, James Cook University, Townsville, Queensland, Australia. Jodie.Morris1@jcu.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22473609

Citation

Morris, Jodie, et al. "Burkholderia Pseudomallei Triggers Altered Inflammatory Profiles in a Whole-blood Model of Type 2 Diabetes-melioidosis Comorbidity." Infection and Immunity, vol. 80, no. 6, 2012, pp. 2089-99.
Morris J, Williams N, Rush C, et al. Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood model of type 2 diabetes-melioidosis comorbidity. Infect Immun. 2012;80(6):2089-99.
Morris, J., Williams, N., Rush, C., Govan, B., Sangla, K., Norton, R., & Ketheesan, N. (2012). Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood model of type 2 diabetes-melioidosis comorbidity. Infection and Immunity, 80(6), 2089-99. https://doi.org/10.1128/IAI.00212-12
Morris J, et al. Burkholderia Pseudomallei Triggers Altered Inflammatory Profiles in a Whole-blood Model of Type 2 Diabetes-melioidosis Comorbidity. Infect Immun. 2012;80(6):2089-99. PubMed PMID: 22473609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood model of type 2 diabetes-melioidosis comorbidity. AU - Morris,Jodie, AU - Williams,Natasha, AU - Rush,Catherine, AU - Govan,Brenda, AU - Sangla,Kunwarjit, AU - Norton,Robert, AU - Ketheesan,Natkunam, Y1 - 2012/04/02/ PY - 2012/4/5/entrez PY - 2012/4/5/pubmed PY - 2012/7/18/medline SP - 2089 EP - 99 JF - Infection and immunity JO - Infect Immun VL - 80 IS - 6 N2 - 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. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/22473609/Burkholderia_pseudomallei_triggers_altered_inflammatory_profiles_in_a_whole_blood_model_of_type_2_diabetes_melioidosis_comorbidity_ L2 - https://journals.asm.org/doi/10.1128/IAI.00212-12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -