Interleukin-1β receptor expressed by modified vaccinia virus Ankara interferes with interleukin-1β activity produced in various virus-infected antigen-presenting cells
1 Division of Virology, Paul-Ehrlich Institute, Langen, Germany
2 Junior Research Group, Novel Vaccination Strategies and Early Immune Responses, Paul-Ehrlich Institute, Langen, Germany
3 President´s Research Group 2, Paul-Ehrlich Institute, Langen, Germany
4 Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Munich, Germany
Virology Journal 2013, 10:34 doi:10.1186/1743-422X-10-34Published: 28 January 2013
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.
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.
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.