Gene-expression profiles in murine melioidosis

Abstract

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is a septicemic illness, often associated with pneumonia and bacterial dissemination to distant sites. Recently we reported the inflammatory mRNA profile in blood leukocytes during human melioidosis. Knowledge of the inflammatory gene expression profile in the pulmonary compartment after infection with B. pseudomallei, however, is highly limited. We therefore aimed to characterize the inflammatory mRNA profile in the pulmonary and systemic compartment during murine melioidosis. By using a newly developed mouse specific Multiplex-Ligation-dependent-Probe-Amplification (MLPA) assay we determined the expression profile of 33 genes encoding inflammatory proteins in lung tissue, leukocytes in bronchoalveolar-lavage-fluid (BALF) and blood leukocytes in mice before and at several time points after intranasal infection with B. pseudomallei. Relative to naïve mice, mice intranasally infected with B. pseudomallei showed increased transcription of a whole array of genes involved in inflammation, Toll-like receptor-signaling, coagulation, fibrinolysis, cell adhesion, tissue repair and homeostasis in the lung, BALF and blood compartment. Notably, many inflammatory genes were shown to be differentially expressed during the course of infection. These data provide new information on compartmentalized inflammatory gene-expression profiles after infection with B. pseudomallei, increasing our insights into the extent of inflammation activation in the pulmonary and systemic compartment during melioidosis.