Role of the Monocyte-Macrophage System in Early Life Cytomegalovirus infection

• Applicant: Professor Felix Stahl, Ph.D.
• Subject Area: Immunology ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390968126

Congenital CMV disease is most likely the result of an altered antiviral immune response in the early life period allowing increased virus replication in the unborn child. Infection of neonatal mice with MCMV serves as an elegant model to study principles of early life anti-CMV immunity. Several experimental approaches identified prominent age-related differences in steady state and during an anti-MCMV response: i) the plasma protein composition, ii) the expression of proteins after MCMV infection, iii) the absolute number of Mo in blood in steady state, iv) the presence of myeloid cells in NIFs, v) the absolute number of naïve T cells, and vi) the expansion of MCMV-specific effector T cells differ significantly between neonatal and adult mice. As normalization of the absolute number of T cells by adoptive T cell transfers into neonates does not rescue these mice from protracted virus infection other factors must be involved in modulation of early life anti-CMV immunity. Cells of the Mo/Mɸ system at the site of infection are likely key players causative for the delayed virus control in neonates. However, it is currently unknown which phenotype these cells adopt in situ in inflamed tissue. Moreover, it is not known if these cells interfere with anti-CMV T cell immunity in NIFs at the priming phase to modulate T cell differentiation or later during the T cell effector phase. Finally, molecules involved in this process and their potential usage for modification are undefined.

• DFG Programme: Research Grants