Microglia are required for protection against lethal coronavirus encephalitis in mice
D. Lori Wheeler, … , David K. Meyerholz, Stanley Perlman
D. Lori Wheeler, … , David K. Meyerholz, Stanley Perlman
Published January 29, 2018
Citation Information: J Clin Invest. 2018;128(3):931-943. https://doi.org/10.1172/JCI97229.
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Research Article Immunology Virology

Microglia are required for protection against lethal coronavirus encephalitis in mice

Abstract

Recent findings have highlighted the role of microglia in orchestrating normal development and refining neural network connectivity in the healthy CNS. Microglia are not only vital cells in maintaining CNS homeostasis, but also respond to injury, infection, and disease by undergoing proliferation and changes in transcription and morphology. A better understanding of the specific role of microglia in responding to viral infection is complicated by the presence of nonmicroglial myeloid cells with potentially overlapping function in the healthy brain and by the rapid infiltration of hematopoietic myeloid cells into the brain in diseased states. Here, we used an inhibitor of colony-stimulating factor 1 receptor (CSF1R) that depletes microglia to examine the specific roles of microglia in response to infection with the mouse hepatitis virus (MHV), a neurotropic coronavirus. Our results show that microglia were required during the early days after infection to limit MHV replication and subsequent morbidity and lethality. Additionally, microglia depletion resulted in ineffective T cell responses. These results reveal nonredundant, critical roles for microglia in the early innate and virus-specific T cell responses and for subsequent host protection from viral encephalitis.

Authors

D. Lori Wheeler, Alan Sariol, David K. Meyerholz, Stanley Perlman

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Figure 4

Delayed virus clearance in microglia-depleted animals.

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Delayed virus clearance in microglia-depleted animals. Mice were treated...
Mice were treated with PLX5622 for 7 days prior to intracranial MHV infection. (A) Brain virus titers were determined on the indicated days p.i. by plaque assay. (B) Protein levels of IFN-α1, IFN-β, and IL-6 in the brain were determined 5 days p.i. (C) Expression levels of viral genomic RNA, IFN-α4, IFN-β, and IL-6 in the brains of infected mice as assessed by qPCR on the indicated days p.i. IFN-I and IL-6 levels generally correlated with those of viral genomic RNA (Table 1). Data represent the mean ± SEM. Data in A were combined from 3 independent experiments, with a combined total of 8 to 11 mice per group. Data shown in B were combined from 2 independent experiments. Data in C are representative of 3 independent experiments, with 10 mice per group. *P < 0.05 and **P < 0.01, by Mann-Whitney U test.