NK/ILC1 Cells Mediate Neuroinflammation and Brain Pathology Following Congenital CMV Infection

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2021 Feb 25

PMID 33630019

Citations 25

Authors

Daria Kvestak

Vanda Juranic Lisnic

Berislav Lisnic

Jelena Tomac

Mijo Golemac

Ilija Brizic

Daniela Indenbirken

Maja Cokaric Brdovcak

Giovanni Bernardini

Fran Krstanovic

Carmen Rozmanic

Adam Grundhoff

Astrid Krmpotic

William J Britt

Stipan Jonjic

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Susceptibility of Mouse Brain to MCMV Infection and Neuroinflammation During Ontogeny.

Krstanovic F, Mihalic A, Sakota L, Lisnic B, Jonjic S, Brizic I Pathogens. 2025; 13(12.

PMID: 39770367 PMC: 11728524. DOI: 10.3390/pathogens13121108.

Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection.

McCord J, Han J, Staudt R, Philp N, Snyder C Sci Adv. 2024; 10(47):eadn6379.

PMID: 39565860 PMC: 11578184. DOI: 10.1126/sciadv.adn6379.

Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring.

Tarhini S, Crespo-Quiles C, Buhler E, Pineau L, Pallesi-Pocachard E, Villain S J Neuroinflammation. 2024; 21(1):298.

PMID: 39548550 PMC: 11566200. DOI: 10.1186/s12974-024-03276-4.

Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection.

Karner D, Kvestak D, Kucan Brlic P, Cokaric Brdovcak M, Lisnic B, Brizic I Nat Commun. 2024; 15(1):7754.

PMID: 39237588 PMC: 11377837. DOI: 10.1038/s41467-024-51931-4.

Immune surveillance of cytomegalovirus in tissues.

Mihalic A, Zeleznjak J, Lisnic B, Jonjic S, Juranic Lisnic V, Brizic I Cell Mol Immunol. 2024; 21(9):959-981.

PMID: 39134803 PMC: 11364667. DOI: 10.1038/s41423-024-01186-2.

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