ArticleJournal of virology2013
Transgenic CCL2 expression in the central nervous system results in a dysregulated immune response and enhanced lethality after coronavirus infection.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Chronic exercise reduces astrocytic c-Fos and CCL2 via conditioned serum and cerebrospinal fluid.Narra J · 2025Article
- Increased CCL2/CCR2 axis promotes tumor progression by increasing M2 macrophages in MYC/BCL2 double-expressor DLBCL.Blood advances · 2024Article
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Opposing effects of apoE2 and apoE4 on microglial activation and lipid metabolism in response to demyelination.Molecular neurodegeneration · 2022Article
- Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice.Journal of virology · 2022Article
- Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis.Frontiers in immunology · 2022Review
- Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice.bioRxiv : the preprint server for biology · 2021Article
- Targeting the CCL2/CCR2 Axis in Cancer Immunotherapy: One Stone, Three Birds?Frontiers in immunology · 2021Review
- Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus.Journal of virology · 2020Article
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- A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction.Brain, behavior, and immunity · 2020Article
- Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis.Acta neuropathologica communications · 2020Article
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- Interferon regulatory factors 3 and 7 have distinct roles in the pathogenesis of alphavirus encephalomyelitis.The Journal of general virology · 2019Article
- The neonatal anti-viral response fails to control measles virus spread in neurons despite interferon-gamma expression and a Th1-like cytokine profile.Journal of neuroimmunology · 2018Article
- Virus-induced inflammasome activation is suppressed by prostaglandin DProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Interferon gamma modulation of disease manifestation and the local antibody response to alphavirus encephalomyelitis.The Journal of general virology · 2016Article
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- MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.Journal of virology · 2016Article
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Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chemokine (C-C motif) ligand 2 (CCL2), a chemoattractant for macrophages, T cells, and cells expressing CCR2, is upregulated during acute and chronic inflammation. CCL2 has been implicated in both proinflammatory and anti-inflammatory responses and has been suggested as a target for therapy in some inflammatory disorders. To examine the role of CCL2 during virus infection, we infected mice transgenically expressing CCL2 in the central nervous system (CCL2 Tg) with an attenuated neurotropic coronavirus (rJ2.2 strain of mouse hepatitis virus). Infection of wild-type mice with rJ2.2 results in mild acute encephalitis, followed by a nonlethal, chronic demyelinating disease. Proinflammatory innate and adaptive immune responses mediate virus clearance. In marked contrast, CCL2 Tg mice infected with rJ2.2 ineffectively cleared virus and rapidly succumbed to the infection. CCL2 Tg mice mounted a dysregulated immune response, characterized by augmented accumulation of regulatory Foxp3(+)CD4(+) T cells and of nitric-oxide- and YM-1-expressing macrophages and microglia, suggestive of mixed M1/M2 macrophage activation. Further, macrophages from infected CCL2 Tg brains relative to non-Tg controls were less activated/mature, expressing lower levels of major histocompatibility complex class II (MHC-II), CD86, and CD40. Collectively, these results show that persistent CCL2 overexpression establishes and sustains an immunological milieu that is both inflammatory and immunosuppressive and predisposes mice to a defective immune response to a minimally lethal virus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.