Innate determinants of protective antiviral immunity in the very young
In this project we will investigate the effects of age on T regulatory cell responses, and pathogen recognition receptor signalling (including surface toll like receptor responses) to important perinatal viral infections.
Viral infections are a major cause of mortality and morbidity in infancy. Understanding the immunological mechanisms that govern protective antiviral immunity in the first weeks of life is critical to the development of neonatal vaccines. Our laboratory uses murine models of neonatal viral infections to define age-dependant differences in neonatal innate and adaptive antiviral immunity.
Investigating how TLR-mediated immunity shapes the adaptive newborn immune response to herpesviruses. DC express Toll-Like Receptors (TLR’s) which when triggered by microbial products induce the expression of immune response genes. HSV-1 and HSV-2 recognise TLR2 and TLR9. Responses of neonatal monocytes and macrophages to multiple TLR ligands including TLR9 are reportedly reduced. We will use mice with targeted gene deletions in TLR2, TLR9 and down stream signalling pathways to test if observed age-dependant differences in innate effector response to HSV are mediated via TLR-9 or TLR-2, and whether manipulation of these pathways represents a strategy to treat newborn viral infections, and induce lifelong adaptive antiviral immunity. Regulatory T cell responses to perinatal viral infections. Results from murine studies of HSV infection in newborn mice suggest that regulatory T cells suppress T cell effector responses in the newborn period, thereby limiting the ability to mount protective immunity. Future studies will confirm findings in human models of important perinatal infections (e.g. from cord blood of infants with Congenital CMV infection, perinatal HSV disease, or perinatal hepatitis C virus infection).
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Herpes simplex virus disease, Congenital infections, Neonatal herpes simplex virus disease, Congenital CMV infection, Perinatal hepatitis C virus infection, Viruses, Dendritic cells, cellular immunity, T regulatory cells, Neonates, Infectious diseases, Infection & immunity
The opportunity ID for this research opportunity is: 77