Response to pathogen-derived nucleic acids
Defining predicators of anti-viral immunity in the yellow fever vaccination model using gene polymorphisms and early innate response patterns (B14)
Project leaders: Prof. Anne Krug and Prof. Simon Rothenfußer
Using the live-attenuated yellow fever virus (YF17D) vaccination as a model of an acute self-limiting RNA virus infection in humans, we will determine how the cooperation of different nucleic acid sensors and antigen presenting cell subpopulations induces early innate responses which are critical for generating effective and long-lasting adaptive immunity. Linking cell-type-specific gene expression with genome-wide SNP analysis in 250 vaccinees will determine expression quantitative trait loci (eQTLs) influencing YF17D-induced gene expression. Thereby we will identify new factors regulating nucleic acid sensing pathways and investigate the genetic basis of inter-individual variability in innate and adaptive antiviral immunity.
Immune sensing of nucleic acids in the pathophysiology of immune complex glomerulonephritis associated with chronic viral infection (B15)
Project leaders: Prof. Dr. Zeinab Abdullah and Prof. Christian Kurts
A common clinical complication in patients with chronic HIV and HCV infections is the development of Immune complex-glomerulonephritis (IC-GN), characterized by enhanced levels of virus ICs, autoantibodies and IFN-I. To identify the pathophysiological cellular and molecular underpinning mechanisms, we will investigate the relevance of sensing nucleic acids from the virus, NETs and dead host cells and the microbiota for autoantibody and IC-GN development using the neo-LCMV infection. Specifically, we will determine the role of RNA and DNA sensing by RIG-like helicases, STING or TLR (7, 9 or 3) in the development of autoantibodies, interferonopathy, and IC-GN development.
