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- Publisher Website: 10.4049/jimmunol.174.6.3534
- Scopus: eid_2-s2.0-14844355133
- PMID: 15749890
- WOS: WOS:000227510900052
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Article: The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis
Title | The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis |
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Authors | |
Issue Date | 2005 |
Citation | Journal of Immunology, 2005, v. 174, n. 6, p. 3534-3544 How to Cite? |
Abstract | IL-12 is a potent inducer of IFN-γ production and promotes a protective cell-mediated immune response after Mycobacterium tuberculosis infection. Recently, the IL-12-related cytokine IL-27 was discovered, and WSX-1 was identified as one component of the IL-27R complex. To determine the functional significance of IL-27/WSX-1 during tuberculosis, we analyzed the course of infection and the immune response in WSX-1-KO mice after aerosol infection with M. tuberculosis. In the absence of WSX-I, an increased production of the proinflammatory cytokines TNF and IL-12p40 resulted in elevated CD4 + T cell activation and IFN-γ production, which enhanced macrophage effector functions and reduced bacterial loads. This is the first occasion of a selectively gene-deficient mouse strain showing higher levels of protective immunity against M. tuberculosis infection than wild-type mice. However, a concomitantly increased chronic inflammatory response also accelerated death of infected WSX-1-KO mice. In vitro, IL-27 induced STAT3 phosphorylation and inhibited TNF and IL-12 production in activated peritoneal macrophages, indicating a novel feedback mechanism by which IL-27 can modulate excessive inflammation. In conclusion, IL-27 both prevents optimal antimycobacterial protection and limits the pathological sequelae of chronic inflammation. Copyright © 2005 by The American Association of Immunologists, Inc. |
Persistent Identifier | http://hdl.handle.net/10722/291690 |
ISSN | 2023 Impact Factor: 3.6 2023 SCImago Journal Rankings: 1.558 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Hölscher, Christoph | - |
dc.contributor.author | Hölscher, Alexandra | - |
dc.contributor.author | Rückerl, Dominik | - |
dc.contributor.author | Yoshimoto, Takayuki | - |
dc.contributor.author | Yoshida, Hiroki | - |
dc.contributor.author | Mak, Tak | - |
dc.contributor.author | Saris, Christiaan | - |
dc.contributor.author | Ehlers, Stefan | - |
dc.date.accessioned | 2020-11-17T14:54:54Z | - |
dc.date.available | 2020-11-17T14:54:54Z | - |
dc.date.issued | 2005 | - |
dc.identifier.citation | Journal of Immunology, 2005, v. 174, n. 6, p. 3534-3544 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291690 | - |
dc.description.abstract | IL-12 is a potent inducer of IFN-γ production and promotes a protective cell-mediated immune response after Mycobacterium tuberculosis infection. Recently, the IL-12-related cytokine IL-27 was discovered, and WSX-1 was identified as one component of the IL-27R complex. To determine the functional significance of IL-27/WSX-1 during tuberculosis, we analyzed the course of infection and the immune response in WSX-1-KO mice after aerosol infection with M. tuberculosis. In the absence of WSX-I, an increased production of the proinflammatory cytokines TNF and IL-12p40 resulted in elevated CD4 + T cell activation and IFN-γ production, which enhanced macrophage effector functions and reduced bacterial loads. This is the first occasion of a selectively gene-deficient mouse strain showing higher levels of protective immunity against M. tuberculosis infection than wild-type mice. However, a concomitantly increased chronic inflammatory response also accelerated death of infected WSX-1-KO mice. In vitro, IL-27 induced STAT3 phosphorylation and inhibited TNF and IL-12 production in activated peritoneal macrophages, indicating a novel feedback mechanism by which IL-27 can modulate excessive inflammation. In conclusion, IL-27 both prevents optimal antimycobacterial protection and limits the pathological sequelae of chronic inflammation. Copyright © 2005 by The American Association of Immunologists, Inc. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Immunology | - |
dc.title | The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.4049/jimmunol.174.6.3534 | - |
dc.identifier.pmid | 15749890 | - |
dc.identifier.scopus | eid_2-s2.0-14844355133 | - |
dc.identifier.volume | 174 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 3534 | - |
dc.identifier.epage | 3544 | - |
dc.identifier.isi | WOS:000227510900052 | - |
dc.identifier.issnl | 0022-1767 | - |