دورية أكاديمية

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation.

التفاصيل البيبلوغرافية
العنوان: Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation.
المؤلفون: DePaula-Silva AB; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA., Gorbea C; Department of Biochemistry, University of Utah, 15 North Medical Drive East, 4100 EEJMRB, Salt Lake City, UT, 84112, USA., Doty DJ; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA., Libbey JE; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA., Sanchez JMS; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA., Hanak TJ; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA., Cazalla D; Department of Biochemistry, University of Utah, 15 North Medical Drive East, 4100 EEJMRB, Salt Lake City, UT, 84112, USA., Fujinami RS; Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT, 84112, USA. Robert.Fujinami@hsc.utah.edu.
المصدر: Journal of neuroinflammation [J Neuroinflammation] 2019 Jul 20; Vol. 16 (1), pp. 152. Date of Electronic Publication: 2019 Jul 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2004-
مواضيع طبية MeSH: Brain/*immunology , Inflammation/*immunology , Macrophages/*immunology , Microglia/*immunology, Animals ; Cardiovirus Infections/immunology ; Mice ; Mice, Inbred C57BL ; Theilovirus/immunology ; Transcription, Genetic ; Transcriptome
مستخلص: Background: In the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking.
Methods: We isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler's murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages.
Results: We have identified and validated new microglial- and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection.
Conclusions: The differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation.
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معلومات مُعتمدة: R01 GM118829 United States GM NIGMS NIH HHS; S10 RR026802 United States RR NCRR NIH HHS; R01 NS091939 United States NS NINDS NIH HHS; P30CA042014 United States CA NCI NIH HHS; T32A1055434 National Institute of Allergy and Infectious Diseases; R01 NS065714 United States NS NINDS NIH HHS; 1S10RR026802 United States NH NIH HHS; R01NS065714 United States NS NINDS NIH HHS; P30 CA042014 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: CNS; Cell surface markers; Cell-specific markers; Immune response; Macrophages; Microglia; Neuroinflammation; RNA-Seq; TMEV; Viral-induced neuroinflammation
تواريخ الأحداث: Date Created: 20190722 Date Completed: 20200113 Latest Revision: 20220716
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6642742
DOI: 10.1186/s12974-019-1545-x
PMID: 31325960
قاعدة البيانات: MEDLINE
الوصف
تدمد:1742-2094
DOI:10.1186/s12974-019-1545-x