Investigating the mechanisms of DC licensing for CTL induction following virus infection

• Applicant: Annabell Bachem
• Subject Area: Immunology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250878614

Cytotoxic CD8+ T cells (CTL) are not only critical for the elimination of virus-infected cells, but also contribute to pathology in chronic virus infections. To improve CTL-based therapeutic interventions against these globally relevant diseases, we need a better understanding of the mechanisms underlying CTL priming by dendritic cells (DC). As DC require activation by innate signals and/or licensing by CD4+ T cells to elicit optimal CTL responses, these two modalities represent key components of CTL immunity. However, how precisely innate signals, such as toll-like receptors (TLR) and interferons (IFN) contribute to CTL immunity and what the mechanistic regulation of CD4+ T cell-mediated DC licensing is, remains poorly understood. Building on unpublished results obtained in a model of Herpes simplex virus (HSV) skin infection, we propose that DC licensing is mediated by CD4+ T cells endowing DC with the ability to provide IL-15 to CTL. It is hypothesized that this mode of DC licensing is not only relevant for murine HSV infection, but also impacts on immunity to other viral infections, such as influenza, and that basic principles predicted from this model also operate in human DC. By elucidating how interferons (type I IFN, IFN-gamma) and toll-like receptors (TLR3) regulate these events, and by validating the relevance of this model in other virus infections and the human setting, we expect this project to advance our understanding of T cell immunity.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Dr. Sammy Bedoui