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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-7-31
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pubmed:abstractText |
Induction of the antiviral cytokine interferon alpha/beta (IFN-alpha/beta) is common in many viral infections. The impact of ongoing antiviral responses on subsequent bacterial infection is not well understood. In human disease, bacterial superinfection complicating a viral infection can result in significant morbidity and mortality. We injected mice with polyinosinic-polycytidylic (PIC) acid, a TLR3 ligand and known IFN-alpha/beta inducer as well as nuclear factor kappaB (NF-kappaB) activator to simulate very early antiviral pathways. We then challenged mice with an in vivo septic shock model characterized by slowly evolving bacterial infection to simulate bacterial superinfection early during a viral infection. Our data demonstrated robust induction of IFN-alpha in serum within 24 h of PIC injection with IFN-alpha/beta-dependent major histocompatibility antigen class II up-regulation on peritoneal macrophages. PIC pretreatment before septic shock resulted in augmented tumor necrosis factor alpha and interleukins 6 and 10 and heightened lethality compared with septic shock alone. Intact IFN-alpha/beta signaling was necessary for augmentation of the inflammatory response to in vivo septic shock and to both TLR2 and TLR4 agonists in vitro. To assess the NF-kappaB contribution to PIC-modulated inflammatory responses to septic shock, we treated with parthenolide, an NF-kappaB inhibitor before PIC and septic shock. Parthenolide did not inhibit IFN-alpha induction by PIC. Inhibition of NF-kappaB by parthenolide did reduce IFN-alpha-mediated potentiation of the cytokine response and lethality from septic shock. Our data demonstrate that pathways activated early during many viral infections can have a detrimental impact on the outcome of subsequent bacterial infection. These pathways may be critical to understanding the heightened morbidity and mortality from bacterial superinfection after viral infection in human disease.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10103303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10227998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10530583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10553091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10569781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10629458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10670840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10762073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-10899117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-11160329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-11420036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-11792059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-11899069,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-11932417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-12035857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-12117955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-12209136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-12679810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-12702806,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-1315357,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-15640628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-15753748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-16034087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-16374373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-2147233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-2199735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-3023797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-3806893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-3895437,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-4302684,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-6347892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-6997619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-7682583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-7715646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-7963712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8379598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8432613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8459215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8608598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8638399,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8895920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-8943414,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9207361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9430659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9590320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9662362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9732873,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9878301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16878028-9916717
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antiviral Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Poly I-C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Interferon alpha-beta,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1073-2322
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
187-94
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pubmed:dateRevised |
2010-9-17
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pubmed:meshHeading |
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