Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis.
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 producti...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
2007
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| _version_ | 1826306790343573504 |
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| author | Wiersinga, W Wieland, C van der Windt, G de Boer, A Florquin, S Dondorp, A Day, N Peacock, S van der Poll, T |
| author_facet | Wiersinga, W Wieland, C van der Windt, G de Boer, A Florquin, S Dondorp, A Day, N Peacock, S van der Poll, T |
| author_sort | Wiersinga, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:53:15Z |
| format | Journal article |
| id | oxford-uuid:fd3e2698-3f8c-4cba-982b-69e05a684b2c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:53:15Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:fd3e2698-3f8c-4cba-982b-69e05a684b2c2022-03-27T13:27:32ZEndogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fd3e2698-3f8c-4cba-982b-69e05a684b2cEnglishSymplectic Elements at Oxford2007Wiersinga, WWieland, Cvan der Windt, Gde Boer, AFlorquin, SDondorp, ADay, NPeacock, Svan der Poll, TMelioidosis 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. |
| spellingShingle | Wiersinga, W Wieland, C van der Windt, G de Boer, A Florquin, S Dondorp, A Day, N Peacock, S van der Poll, T Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title | Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title_full | Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title_fullStr | Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title_full_unstemmed | Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title_short | Endogenous interleukin-18 improves the early antimicrobial host response in severe melioidosis. |
| title_sort | endogenous interleukin 18 improves the early antimicrobial host response in severe melioidosis |
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