Interleukin-1β receptor expressed by modified vaccinia virus Ankara interferes with interleukin-1β activity produced in various virus-infected antigen-presenting cells

Virology Journal

Astrid Schwantes⁴  Gerd Sutter¹  Theresa Resch²  Zoe Waibler²  Stefan Zimmerling³ 

[1] Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Munich, Germany;Junior Research Group, Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich Institute, Langen, Germany;Division of Virology, Paul-Ehrlich Institute, Langen, Germany;President´s Research Group 2, Paul-Ehrlich Institute, Langen, Germany

关键词: Dendritic cells;    Macrophages;    Human cells;    Caspase-1;    Inflammasome;    Viral interleukin-1β receptor;    Interleukin-1β induction;    Modified vaccinia virus Ankara;   

Others  :  1152157
DOI  :  10.1186/1743-422X-10-34

 received in 2012-09-02, accepted in 2013-01-23,  发布年份 2013

【 摘 要 】

Background

Modified vaccinia virus Ankara (MVA) is a highly attenuated virus and a promising vaccine vector with potent immune stimulating properties. Deletion of the gene encoding the viral interleukin-1beta receptor (vIL-1βR) in MVA (MVAΔIL-1βR) was previously shown to enhance memory T cell function. Here, we investigated the influence of vIL-1βR on blocking interleukin-1beta (IL-1β) upon MVA infection in various antigen presenting cells of murine and human origin, and analyzed whether inflammasome function contributes to IL-1β production in different cell types.

Findings

Extending previous studies, immunizing mice with low doses of MVAΔIL-1βR still showed enhanced memory CD8⁺ T cell activation compared to MVA wild-type (MVAwt) immunization. In vitro, murine myeloid dendritic cells, and activated, but not naive primary macrophages were identified as potent producers of IL-1β upon infection with MVA. Importantly, free IL-1β was only detected in the absence of vIL-1βR. Moreover, MVAΔIL-1βR increased amounts of bioactive IL-1β compared to MVAwt after infection of human THP-1 cells, as detected using a reporter system that only responds to active and free IL-1β. The MVA-mediated induction of IL-1β was confirmed to depend on inflammasome function in human and murine cells, however in murine cells this apparently involves caspase-1-independent pathways.

Conclusions

MVA lacking IL-1β blocking activity leads to increased concentrations of free IL-1β upon infection of murine and human antigen presenting cells; this is likely responsible for enhanced memory T cell activation upon MVAΔIL-1βR immunization of mice. Moreover, our results suggest that MVA-mediated IL-1β induction is a multifactorial process.

【 授权许可】

   
2013 Zimmerling et al.; licensee BioMed Central Ltd.

【 图 表 】

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