Tumor necrosis factor-alpha and interleukin-1 beta play a critical role in the resistance against lethal herpes simplex virus encephalitis |
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Authors: | Sergerie Yan Rivest Serge Boivin Guy |
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Institution: | Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Quebec-Centre Hospitalier de l'Universite Laval, Laval University, Quebec City, Quebec, Canada. |
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Abstract: | BACKGROUND: The innate immune response after herpes simplex type 1 (HSV-1) encephalitis could be protective or, paradoxically, implicated in neuronal damage. We investigated the role of the innate immune response in such infection using a C57BL/6 mouse knockout (KO) model for tumor necrosis factor (TNF)-alpha and/or interleukin (IL)-1beta. METHODS: Encephalitis was induced by intranasal infection with a clinical strain of HSV-1 in 1-month-old KO or wild-type (WT) mice. Mice were monitored for survival, brain viral load was quantified by real-time polymerase chain reaction, and the inflammatory response was assessed by in situ hybridization in groups of mice killed on days 3-7. RESULTS: WT mice had a significantly higher mean life expectancy (P=.0001, log-rank test) than other groups. IL-1beta and TNF-alpha KO mice had a similar mean life expectancy, and encephalitis was lethal to all TNF-alpha /IL-1beta-deficient mice. Brain viral loads were lower in WT than in KO mice that had disseminated viral replication in the pons and medulla. Moreover, TNF- alpha and IL-1beta KO mice failed to initiate an adequate immune response, as shown by the virtual absence of expression of proinflammatory molecules in the brain. CONCLUSION: These data clearly demonstrate the importance of TNF-alpha and IL-1beta in protection against HSV-1 encephalitis in this mouse model. |
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