Cellular source of interferon-β in virus-infected organs of mice
Interferon (IFN)-β contributes substantially to innate immunity in mammalian hosts, but information about the in vivo source of this cytokine after pathogen infection remains incomplete. To identify the cell types responsible for IFN-β production during viral infection, we are employing a reporter mouse which expresses firefly luciferase under control of the IFN-β promoter (see figure) and stain organ sections of virus-infected mice with luciferase-specific antibodies. We further use conditional reporter mice that express the luciferase reporter gene solely in defined cell types, such as neurons, astrocytes, microglia and macrophages, or epithelial cells.
Visualization of luciferase gene expression in IFN-β reporter mice infected with La Crosse virus. (Figure from Lienenklaus et al. 2009)
Open questions presently being investigated include:
a) Which cells types express IFN-β in the brain of mice infected with wild-type or mutant La Crosse virus lacking IFN antagonistic factor NSs?
b) Which cells types express IFN-β in the influenza virus-infected lung?
Selected Publications from our group
- Lienenklaus S, Cornitescu M, Zietara N, Gekara N, Jablonska J, Edenhofer F, Bruder K, Hafner M, Staeheli P, Weiss S. Novel reporter mouse reveals constitutive and inflammatory expression of IFN-β in vivo. J. Immunol. 183: 3229-3236 (2009)
- Kaminski, M., Ohnemus, A., Cornitescu, M. & P. Staeheli. Plasmacytoid dendritic cells and TLR7-dependent signaling promote efficient protection of mice against highly virulent influenza A virus. J. Gen. Virol. 93: 555-559 (2012)
- Ganal, S.C., Sanos, S.L., Kallfass, C., Oberle, K., Johner, C., Kirschnig, C., Lienenklaus, S., Weiss, S., Staeheli, P., Aichele, P., & A. Diefenbach. Priming of natural killer cells by non-mucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37: 171-186 (2012)
- Kallfass, C., Ackerman, A., Lienenklaus, S., Weiss, S., Heimrich, B., & P. Staeheli. Visualizing production of interferon-β by astrocytes and microglia in the brain of La Crosse virus-infected mice. J. Virol. 86: 11223-11230 (2012)
- Kallfass, C., Lienenklaus, S., Weiss, S., & P. Staeheli. Visualizing the interferon-β response in mice during infection with influenza A viruses expressing or lacking nonstructural protein 1. J. Virol. 87: 6925-6930 (2013)
Collaboration
Dr. Stefan Lienenklaus and Dr. Sigmund Weiß, HZI, Braunschweig
Prof. Andreas Diefenbach, University Medical Center Freiburg
Prof. Thomas Michiels, Brussels
Prof. Klaus Conzelmann, Munich