engleski

Perinatal mouse cytomegalovirus infection induces activation of brain resident microglial cells and recruitment of inflammatory cells into the brain

Congenital human cytomegalovirus (HCMV) infection is the most common viral cause of long-term neurodevelopmental sequelae, including microcephaly and sensorineural hearing loss. As HCMV does not cross the species barrier, we employed a mouse model in which newborn mice are infected by intraperitoneal (i.p.) inoculation of mouse cytomegalovirus (MCMV). Following infection the virus disseminates to the central nervous system (CNS) and replicates in the brain parenchyma. CNS infection leads to the activation of resident microglial cells and the recruitment of peripheral immune cells. In addition, the virus induces delay in cerebellar growth. In our model of congenital MCMV infection, the initial neuroimmune responses are dominated by activation of resident microglial cells and the influx of NK cells, whose appearance coincides with detection of the virus in the brain. The number of NK cells in the CNS peaked at day 8 post infection (p.i.). In addition, we also observed recruitment of other peripheral immune cells, of which CD8+ T cells were the most numerous and peaked on day 21 p.i. Phenotypic analysis showed that MCMV-specific CD8+ T cells are highly activated and display tissue resident memory phenotype during latency. Our results demonstrated the coordinated action of innate and acquired immunity in the clearance of congenital MCMV infection of the brain. Furthermore, the results demonstrated the functional role of antigen-specific CD8+ T cells in protection from virus-induced pathology in the neonatal CNS.

congenital cytomegalovirus infection; microglia; NK cells; CD8+ T cells

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