Naslov
NK/ILC1 cells mediate neuroinflammation and brain pathology following congenital CMV infection

Autori
Kveštak, Daria ; Juranić Lisnić, Vanda ; Lisnić, Berislav ; Tomac, Jelena ; Golemac, Mijo ; Brizić, Ilija ; Indenbirken, Daniela ; Cokarić Brdovčak, Maja ; Bernardini, Giovanni ; Krstanović, Fran ; Rožmanić, Carmen ; Grundhoff, Adam ; Krmpotić, Astrid ; Britt, William J ; Jonjić, Stipan

Izvornik
The Journal of experimental medicine (0022-1007) 218 (2021), 5; 1-14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
congenital infection, nk cells, cytomegalovirus, ILC1 cells, brain pathology

Sažetak
Congenital human cytomegalovirus (cHCMV) infection of the brain is associated with a wide range of neurocognitive sequelae. Using infection of newborn mice with mouse cytomegalovirus (MCMV) as a reliable model that recapitulates many aspects of cHCMV infection, including disseminated infection, CNS infection, altered neurodevelopment, and sensorineural hearing loss, we have previously shown that mitigation of inflammation prevented alterations in cerebellar development, suggesting that host inflammatory factors are key drivers of neurodevelopmental defects. Here, we show that MCMV infection causes a dramatic increase in the expression of the microglia-derived chemokines CXCL9/CXCL10, which recruit NK and ILC1 cells into the brain in a CXCR3-dependent manner. Surprisingly, brain-infiltrating innate immune cells not only were unable to control virus infection in the brain but also orchestrated pathological inflammatory responses, which lead to delays in cerebellar morphogenesis. Our results identify NK and ILC1 cells as the major mediators of immunopathology in response to virus infection in the developing CNS, which can be prevented by anti-IFN-γ antibodies.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA