Journal article
Differential Effects of Prostaglandin D 2 Signaling on Macrophages and Microglia in Murine Coronavirus Encephalomyelitis
mBio, Vol.12(5), e01969-21
10/26/2021
DOI: 10.1128/mBio.01969-21
PMCID: PMC8546556
PMID: 34488442
Abstract
Current understanding about the roles of microglia versus macrophages in viral encephalitis is limited. We previously showed that the signaling of a single prostaglandin, PGD 2 , through its DP1 receptor on myeloid cells is critical for optimal immune responses in infected mice.
ABSTRACT Microglia and macrophages initiate and orchestrate the innate immune response to central nervous system (CNS) virus infections. Microglia initiate neurotropic coronavirus clearance from the CNS, but the role of infiltrating macrophages is not well understood. Here, using mice lacking cell-specific expression of DP1, the receptor for prostaglandin D 2 (PGD 2 ), we delineate the relative roles of PGD 2 signaling in microglia and macrophages in murine coronavirus-infected mice. We show that the absence of PGD 2 /DP1 signaling on microglia recapitulated the suboptimal immune response observed in global DP1 −/− mice. Unexpectedly, the absence of the DP1 receptor on macrophages had an opposite effect, resulting in enhanced activation and more rapid virus clearance. However, microglia are still required for disease resolution, even when macrophages are highly activated, in part because they are required for macrophage recruitment to sites of infection. Together, these results identify key differences in the effects of PGD 2 /DP1 signaling on microglia and macrophages and illustrate the complex relationship between the two types of myeloid cells. IMPORTANCE Current understanding about the roles of microglia versus macrophages in viral encephalitis is limited. We previously showed that the signaling of a single prostaglandin, PGD 2 , through its DP1 receptor on myeloid cells is critical for optimal immune responses in infected mice. Here, we demonstrate that the specific ablation of the DP1 receptor on macrophages and microglia had markedly different effects on outcomes. DP1 −/− macrophages exhibited greater phagocytic properties than controls, resulting in enhanced kinetics of virus clearance, while DP1 absence on microglia resulted in increased lethality. Microglia were still required for protection, even when DP1 was not expressed on macrophages. These results suggest that therapeutic strategies directed at specific myeloid subsets in the brain may be useful in the context of viral infections.
Details
- Title: Subtitle
- Differential Effects of Prostaglandin D 2 Signaling on Macrophages and Microglia in Murine Coronavirus Encephalomyelitis
- Creators
- Abhishek Kumar Verma - University of IowaJian Zheng - University of IowaMatthias Mack - University Hospital RegensburgFlorent Ginhoux - Agency for Science, Technology and ResearchStanley Perlman - University of Iowa
- Contributors
- Diane E Griffin (Editor)
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.12(5), e01969-21
- DOI
- 10.1128/mBio.01969-21
- PMID
- 34488442
- PMCID
- PMC8546556
- NLM abbreviation
- mBio
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Grant note
- DOI: 10.13039/100007197, name: HHS | U.S. Public Health Service, award: RO1 NS36592; DOI: 10.13039/100000890, name: National Multiple Sclerosis Society, award: RG 5340-A-7
- Language
- English
- Date published
- 10/26/2021
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984187038802771
Metrics
25 Record Views