Naslov
Characterization of microglial and CD8+ T cell response in brain following congenital MCMV infection

Autori
Arapović, Jurica ; Arapović, Maja ; Kveštak, Daria ; Csaba Huszthy, Peter ; Golemac, Mijo ; Pernjak Pugel, Ester ; Torti, Nicole ; Oxenius, Annette ; Krmpotić, Astrid ; Britt, William J. ; Jonjić, Stipan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Regulatory myeloid cells (MRC) in health and disease

Mjesto i datum
Kraków, Poljska, 2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Congenital cytomegalovirus infection; microglia; CD8

Sažetak
Congenital human cytomegalovirus (HCMV) infection is the most common cause of long-term neurodevelopmental sequelae, including mental retardation 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 i.p. inoculation of newborn mice, the virus disseminates to the CNS and replicates in the brain parenchyma. Histological analysis revealed virus-induced cellular changes in the brain, including perivascular- and tissue-infiltrating leukocytes. In addition, we observed a virus-induced retardation in cerebellum growth, and delay in granular neuron migration. CNS infection is coupled with the activation of resident microglial cells and the recruitment of peripheral immune cells, of which CD8+ T cells were the most numerous and peaked on day 21 post infection. We observed persistent polarization of microglial cells toward proinflammatory phenotype which is characterized by upregulation of MHC class I and II molecules, iNOS and TNFa production. Phenotypic analysis also showed that MCMV-specific CD8+ T cells are highly activated and display tissue resident memory phenotype. Furthermore, by adoptive transfer of CD8+ T cells from MHC class I-restricted TCR transgenic mice with specificity for the MCMV-derived epitope M38, we demonstrate that upon MCMV infection, CD8+ T cells migrated from the periphery to the newborn mouse brain. Additional experiments are required to clarify the mechanisms by which brain-resident memory CD8+ T cells are maintained during persistent MCMV infection and the potential role of activated microglial cells in this proces.

Izvorni jezik
Engleski

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