W. Joost WiersingaCatharina W. WielandGerritje J.W. Van Der WindtAnita De BoerSandrine FlorquinArjen DondorpNicholas P. DaySharon J. PeacockTom Van Der PollAcademic Medical Centre, University of AmsterdamMahidol UniversityNuffield Department of Clinical Medicine2018-08-242018-08-242007-08-01Infection and Immunity. Vol.75, No.8 (2007), 3739-3746001995672-s2.0-34547633851https://repository.li.mahidol.ac.th/handle/20.500.14594/24527Melioidosis 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-γ) seems to play an obligatory role in host defense. Previously, we have shown that IFN-γ 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1128/IAI.00080-07