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Melioidosis is caused by the soil saprophyte Burkholderia pseudomallei and is endemic in Southeast Asia. The pathogenesis of melioidosis is still largely unknown, although gamma interferon (IFN-gamma) seems to play an obligatory role in host defense. Previously, we have shown that IFN-gamma production in melioidosis is controlled in part by interleukin-18 (IL-18). The aim of the present study was to determine the role of IL-18 in the immune response to B. pseudomallei. For this the following investigations were performed. (i) Plasma IL-18 and blood monocyte IL-18 mRNA levels were elevated in 34 patients with culture-proven melioidosis compared to the levels in 32 local healthy controls; in addition, IL-18 binding protein levels were markedly elevated in patients, strongly correlating with mortality. (ii) IL-18 gene-deficient (IL-18 knockout [KO]) mice showed accelerated mortality after intranasal infection with a lethal dose of B. pseudomallei, which was accompanied by enhanced bacterial growth in their lungs, livers, spleens, kidneys, and blood at 24 and 48 h postinfection, compared to wild-type mice. In addition, IL-18 KO mice displayed evidence of enhanced hepatocellular injury and renal insufficiency. Together, these data indicate that the enhanced production of IL-18 in melioidosis is an essential part of a protective immune response to this severe infection.

Original publication

DOI

10.1128/IAI.00080-07

Type

Journal article

Journal

Infect Immun

Publication Date

08/2007

Volume

75

Pages

3739 - 3746

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Animals, Blood, Burkholderia pseudomallei, Colony Count, Microbial, Disease Models, Animal, Female, Histocytochemistry, Humans, Intercellular Signaling Peptides and Proteins, Interleukin-18, Kidney, Liver, Lung, Male, Melioidosis, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Monocytes, RNA, Messenger, Spleen, Survival Analysis, Thailand