Delayed activation of host innate immune pathways in streptozotocin-induced diabetic hosts leads to more severe disease during infection with Burkholderia pseudomallei

Chui Yoke Chin, Denise M. Monack, Sheila Nathan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Diabetes mellitus is a predisposing factor of melioidosis, contributing to higher mortality rates in diabetics infected with Burkholderia pseudomallei. To investigate how diabetes alters the inflammatory response, we established a streptozotocin (STZ) -induced diabetic murine acute-phase melioidosis model. Viable B. pseudomallei cells were consistently detected in the blood, liver and spleen during the 42-hr course of infection but the hyperglycaemic environment did not increase the bacterial burden. However, after 24hr, granulocyte counts increased in response to infection, whereas blood glucose concentrations decreased over the course of infection. A genome-wide expression analysis of the STZ-diabetic murine acute melioidosis liver identified ∼1000 genes whose expression was altered in the STZ-diabetic mice. The STZ-diabetic host transcriptional response was compared with the normoglycaemic host transcriptional response recently reported by our group. The microarray data suggest that the presence of elevated glucose levels impairs the host innate immune system by delaying the identification and recognition of B. pseudomallei surface structures. Consequently, the host is unable to activate the appropriate innate immune response over time, which may explain the increased susceptibility to melioidosis in the STZ-diabetic host. Nevertheless, a general 'alarm signal' of infection as well as defence programmes are still triggered by the STZ-diabetic host, although only 24hr after infection. In summary, this study demonstrates that in the face of a B. pseudomallei acute infection, poor glycaemic control impaired innate responses during the early stages of B. pseudomallei infection, contributing to the increased susceptibility of STZ-induced diabetics to this fatal disease.

Original languageEnglish
Pages (from-to)312-332
Number of pages21
JournalImmunology
Volume135
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Burkholderia pseudomallei
Streptozocin
Melioidosis
Infection
Liver
Granulocytes
Innate Immunity
Causality
Blood Glucose
Immune System
Diabetes Mellitus
Spleen
Genome
Gene Expression
Glucose
Mortality

Keywords

  • Acute melioidosis
  • Burkholderia pseudomallei
  • Diabetes
  • Hyperglycaemia
  • Innate immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Delayed activation of host innate immune pathways in streptozotocin-induced diabetic hosts leads to more severe disease during infection with Burkholderia pseudomallei. / Chin, Chui Yoke; Monack, Denise M.; Nathan, Sheila.

In: Immunology, Vol. 135, No. 4, 04.2012, p. 312-332.

Research output: Contribution to journalArticle

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