Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells.
BACKGROUND:The type-1 cytokine pathway plays a pivotal role in immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the prod...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2791865?pdf=render |
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| author | Diederik van de Wetering Roelof A de Paus Jaap T van Dissel Esther van de Vosse |
| author_facet | Diederik van de Wetering Roelof A de Paus Jaap T van Dissel Esther van de Vosse |
| author_sort | Diederik van de Wetering |
| collection | DOAJ |
| description | BACKGROUND:The type-1 cytokine pathway plays a pivotal role in immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the production of cytokines that activate lymphocytes to produce interferon (IFN)-gamma. Interleukin (IL)-12 and IL-23 are thought to be the key cytokines required for initiating a type-1 cytokine immune response to Mycobacteria and Salmonellae. The relative contribution of IL-23 and IL-12 to this process is uncertain. METHODOLOGY/PRINCIPAL FINDINGS:We show that various TLR agonists induce the production of IL-23 but not IL-12 in freshly isolated human monocytes and cultured human macrophages. In addition, type 1 pro-inflammatory macrophages (Mphi1) differentiated in the presence of GM-CSF and infected with live Salmonella produce IL-23, IL-1beta and IL-18, but not IL-12. Supernatants of Salmonella-infected Mphi1 contained more IL-18 and IL-1beta as compared with supernatants of Mphi1 stimulated with isolated TLR agonists, and induced IFN-gamma production in human CD56(+) cells in an IL-23 and IL-1beta-dependent but IL-12-independent manner. In addition, IL-23 together with IL-18 or IL-1beta led to the production of GM-CSF in CD56(+) cells. Both IFN-gamma and GM-CSF enhanced IL-23 production by monocytes in response to TLR agonists, as well as induced IL-12 production. CONCLUSIONS/SIGNIFICANCE:The findings implicate a positive feedback loop in which IL-23 can enhance its release via induction of IFN-gamma and GM-CSF. The IL-23 induced cytokines allow for the subsequent production of IL-12 and amplify the IFN-gamma production in the type-1 cytokine pathway. |
| first_indexed | 2024-12-21T17:32:11Z |
| format | Article |
| id | doaj.art-3fbb3d534ae746acbb2f7eb6662a8acf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T17:32:11Z |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3fbb3d534ae746acbb2f7eb6662a8acf2022-12-21T18:55:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e839610.1371/journal.pone.0008396Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells.Diederik van de WeteringRoelof A de PausJaap T van DisselEsther van de VosseBACKGROUND:The type-1 cytokine pathway plays a pivotal role in immunity against intracellular bacterial pathogens such as Salmonellae and Mycobacteria. Bacterial stimulation of pattern recognition receptors on monocytes, macrophages and dendritic cells initiates this pathway, and results in the production of cytokines that activate lymphocytes to produce interferon (IFN)-gamma. Interleukin (IL)-12 and IL-23 are thought to be the key cytokines required for initiating a type-1 cytokine immune response to Mycobacteria and Salmonellae. The relative contribution of IL-23 and IL-12 to this process is uncertain. METHODOLOGY/PRINCIPAL FINDINGS:We show that various TLR agonists induce the production of IL-23 but not IL-12 in freshly isolated human monocytes and cultured human macrophages. In addition, type 1 pro-inflammatory macrophages (Mphi1) differentiated in the presence of GM-CSF and infected with live Salmonella produce IL-23, IL-1beta and IL-18, but not IL-12. Supernatants of Salmonella-infected Mphi1 contained more IL-18 and IL-1beta as compared with supernatants of Mphi1 stimulated with isolated TLR agonists, and induced IFN-gamma production in human CD56(+) cells in an IL-23 and IL-1beta-dependent but IL-12-independent manner. In addition, IL-23 together with IL-18 or IL-1beta led to the production of GM-CSF in CD56(+) cells. Both IFN-gamma and GM-CSF enhanced IL-23 production by monocytes in response to TLR agonists, as well as induced IL-12 production. CONCLUSIONS/SIGNIFICANCE:The findings implicate a positive feedback loop in which IL-23 can enhance its release via induction of IFN-gamma and GM-CSF. The IL-23 induced cytokines allow for the subsequent production of IL-12 and amplify the IFN-gamma production in the type-1 cytokine pathway.http://europepmc.org/articles/PMC2791865?pdf=render |
| spellingShingle | Diederik van de Wetering Roelof A de Paus Jaap T van Dissel Esther van de Vosse Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. PLoS ONE |
| title | Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. |
| title_full | Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. |
| title_fullStr | Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. |
| title_full_unstemmed | Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. |
| title_short | Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells. |
| title_sort | salmonella induced il 23 and il 1beta allow for il 12 production by monocytes and mphi1 through induction of ifn gamma in cd56 nk nk like t cells |
| url | http://europepmc.org/articles/PMC2791865?pdf=render |
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