title: Immune profiling of the progression of a BALB/c mouse aerosol infection by Burkholderia pseudomallei and the therapeutic implications of targeting HMGB1.
abstract: BACKGROUND
  The role of damage-associated molecular pattern HMGB1 signalling in a murine BALB/c model of severe respiratory melioidosis (Burkholderia pseudomallei infection) was explored in this study.
  
  
  METHODS
  Time course experiments were performed.
  
  
  RESULTS
  It was established that HMGB1 was released in concert with increasing weight of organs and increasing concentration of liver enzymes in the blood a short time after cytokine release. Differences in the cytokine response between organs were observed, where the lungs contained higher concentrations of chemokines and interleukin 17, while the spleen produced more interferon-gamma, which is essential in the host defence against B. pseudomallei. This is evidence as to why the disease is seemingly more severe in the respiratory form. The effect of depleting HMGB1 using an antibody was also evaluated. It was found that this treatment significantly reduced bacterial load in the liver, spleen, and, to a greater degree, in the lungs. Cytokine quantification indicated that this reduction in bacterial load is likely due to the treatment reducing the release of a variety of pro-inflammatory cytokines.
  
  
  CONCLUSIONS
  It is concluded that anti-HMGB1 treatment would be effective alongside other therapeutics, where it would reduce the characteristic over-inflammation associated with late stage infection.
authors.affiliation: Biomedical Sciences, DSTL Porton Down, Salisbury, SP4 0JQ, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.affiliation: Biomedical Sciences, DSTL Porton Down, Salisbury, SP4 0JQ, UK.
authors.forename: Graeme C
authors.initials: GC
authors.lastname: Clark
authors.affiliation: Biomedical Sciences, DSTL Porton Down, Salisbury, SP4 0JQ, UK. Electronic address: rvdelia@dstl.gov.uk.
authors.forename: Riccardo V
authors.initials: RV
authors.lastname: D'Elia
mesh_terms: D000336:Aerosols; D000818:Animals; D016957:Burkholderia pseudomallei; D016207:Cytokines; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000627:therapeutic use; D008099:Liver / Q000276:immunology; D008554:Melioidosis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction; D013154:Spleen / Q000382:microbiology
chemical_list: D000336:Aerosols; D016207:Cytokines; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D007371:Interferon-gamma
keywords: Burkholderia pseudomallei; Cytokines; HMGB1; Infection; Mice