MyD88 signaling by neurons induces chemokines that recruit protective leukocytes to the virus-infected CNS

Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-β in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed tha...

Full description

Saved in:
Bibliographic Details
Published in:Science immunology 2021-06, Vol.6 (60)
Main Authors: Ghita, Luca, Spanier, Julia, Chhatbar, Chintan, Mulenge, Felix, Pavlou, Andreas, Larsen, Pia-Katharina, Waltl, Inken, Lueder, Yvonne, Kohls, Moritz, Jung, Klaus, Best, Sonja M, Förster, Reinhold, Stangel, Martin, Schreiner, Dietmar, Kalinke, Ulrich
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport - genetics
Adaptor Proteins, Vesicular Transport - metabolism
Animals
CD8-Positive T-Lymphocytes - immunology
Chemokines - metabolism
Disease Models, Animal
Encephalitis, Viral - immunology
Encephalitis, Viral - pathology
Encephalitis, Viral - virology
Female
Humans
Male
Mice
Mice, Knockout
Myeloid Differentiation Factor 88 - genetics
Myeloid Differentiation Factor 88 - metabolism
Neurons - metabolism
Olfactory Bulb - cytology
Olfactory Bulb - immunology
Olfactory Bulb - pathology
Olfactory Bulb - virology
Rhabdoviridae Infections - immunology
Rhabdoviridae Infections - pathology
Rhabdoviridae Infections - virology
Signal Transduction - immunology
Vesiculovirus - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Viral encephalitis initiates a series of immunological events in the brain that can lead to brain damage and death. Astrocytes express IFN-β in response to neurotropic infection, whereas activated microglia produce proinflammatory cytokines and accumulate at sites of infection. Here, we observed that neurotropic vesicular stomatitis virus (VSV) infection causes recruitment of leukocytes into the central nervous system (CNS), which requires MyD88, an adaptor of Toll-like receptor and interleukin-1 receptor signaling. Infiltrating leukocytes, and in particular CD8 T cells, protected against lethal VSV infection of the CNS. Reconstitution of MyD88, specifically in neurons, restored chemokine production in the olfactory bulb as well as leukocyte recruitment into the infected CNS and enhanced survival. Comparative analysis of the translatome of neurons and astrocytes verified neurons as the critical source of chemokines, which regulated leukocyte infiltration of the infected brain and affected survival.
ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.abc9165