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Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity.
Infect Immun. 2013 Feb; 81(2):470-7.II

Abstract

Bacterial infections are a common and serious complication of type 2 diabetes (T2D). The prevalence of melioidosis, an emerging tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is increased in people with T2D. This is the first study to compare murine models of T2D and melioidosis. Susceptibility and disease progression following infection with B. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic model of T2D. The metabolic profile of mice with diet-induced diabetes, including body weight, blood glucose, cholesterol, triglycerides, insulin resistance, and baseline levels of inflammation, closely resembled that of clinical T2D. Following subcutaneous infection with B. pseudomallei, bacterial loads at 24 and 72 h postinfection in the blood, spleen, liver, lungs, and subcutaneous adipose tissue (SAT) at the site of infection were compared in parallel with the expression of inflammatory cytokines and tissue histology. As early as 24 h postinfection, the expression of inflammatory (interleukin-1β [IL-1β], tumor necrosis factor alpha [TNF-α], and IL-6) and T(H)1 (IL-12 and gamma interferon [IFN-γ]) cytokines was impaired in diabetic mice compared to nondiabetic littermates. Early differences in cytokine expression were associated with excessive infiltration of polymorphonuclear neutrophils (PMN) in diabetic mice compared to nondiabetic littermates. This was accompanied by bacteremia, hematogenous dissemination of bacteria to the lungs, and uncontrolled bacterial growth in the spleens of diabetic mice by 72 h postinfection. The findings from our novel model of T2D and melioidosis comorbidity support the role of impaired early immune pathways in the increased susceptibility of individuals with T2D to bacterial infections.

Authors+Show Affiliations

Infectious Diseases and Immunopathogenesis Research Group, School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland, Australia. Kelly.Hodgson@my.jcu.edu.auNo 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

23208607

Citation

Hodgson, Kelly A., et al. "Impaired Early Cytokine Responses at the Site of Infection in a Murine Model of Type 2 Diabetes and Melioidosis Comorbidity." Infection and Immunity, vol. 81, no. 2, 2013, pp. 470-7.
Hodgson KA, Govan BL, Walduck AK, et al. Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity. Infect Immun. 2013;81(2):470-7.
Hodgson, K. A., Govan, B. L., Walduck, A. K., Ketheesan, N., & Morris, J. L. (2013). Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity. Infection and Immunity, 81(2), 470-7. https://doi.org/10.1128/IAI.00930-12
Hodgson KA, et al. Impaired Early Cytokine Responses at the Site of Infection in a Murine Model of Type 2 Diabetes and Melioidosis Comorbidity. Infect Immun. 2013;81(2):470-7. PubMed PMID: 23208607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity. AU - Hodgson,Kelly A, AU - Govan,Brenda L, AU - Walduck,Anna K, AU - Ketheesan,Natkunam, AU - Morris,Jodie L, Y1 - 2012/12/03/ PY - 2012/12/5/entrez PY - 2012/12/5/pubmed PY - 2013/6/6/medline SP - 470 EP - 7 JF - Infection and immunity JO - Infect Immun VL - 81 IS - 2 N2 - Bacterial infections are a common and serious complication of type 2 diabetes (T2D). The prevalence of melioidosis, an emerging tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, is increased in people with T2D. This is the first study to compare murine models of T2D and melioidosis. Susceptibility and disease progression following infection with B. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic model of T2D. The metabolic profile of mice with diet-induced diabetes, including body weight, blood glucose, cholesterol, triglycerides, insulin resistance, and baseline levels of inflammation, closely resembled that of clinical T2D. Following subcutaneous infection with B. pseudomallei, bacterial loads at 24 and 72 h postinfection in the blood, spleen, liver, lungs, and subcutaneous adipose tissue (SAT) at the site of infection were compared in parallel with the expression of inflammatory cytokines and tissue histology. As early as 24 h postinfection, the expression of inflammatory (interleukin-1β [IL-1β], tumor necrosis factor alpha [TNF-α], and IL-6) and T(H)1 (IL-12 and gamma interferon [IFN-γ]) cytokines was impaired in diabetic mice compared to nondiabetic littermates. Early differences in cytokine expression were associated with excessive infiltration of polymorphonuclear neutrophils (PMN) in diabetic mice compared to nondiabetic littermates. This was accompanied by bacteremia, hematogenous dissemination of bacteria to the lungs, and uncontrolled bacterial growth in the spleens of diabetic mice by 72 h postinfection. The findings from our novel model of T2D and melioidosis comorbidity support the role of impaired early immune pathways in the increased susceptibility of individuals with T2D to bacterial infections. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/23208607/Impaired_early_cytokine_responses_at_the_site_of_infection_in_a_murine_model_of_type_2_diabetes_and_melioidosis_comorbidity_ L2 - https://journals.asm.org/doi/10.1128/IAI.00930-12?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -