دورية أكاديمية
Dendritic cells, macrophages, NK and CD8 + T lymphocytes play pivotal roles in controlling HSV-1 in the trigeminal ganglia by producing IL1-beta, iNOS and granzyme B.
العنوان: | Dendritic cells, macrophages, NK and CD8 + T lymphocytes play pivotal roles in controlling HSV-1 in the trigeminal ganglia by producing IL1-beta, iNOS and granzyme B. |
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المؤلفون: | Lucinda N; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Figueiredo MM; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Pessoa NL; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Santos BS; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Lima GK; Escola de Veterinária, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, 31270-901, MG, Brazil., Freitas AM; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Machado AM; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Kroon EG; Laboratório de Vírus, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, 31270-901, MG, Brazil., Antonelli LR; Biologia e Imunologia Parasitária, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil., Campos MA; Imunologia de Doenças Virais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Avenida Augusto de Lima 1715, Belo Horizonte, 30190-002, MG, Brazil. marcoasc@cpqrr.fiocruz.br. |
المصدر: | Virology journal [Virol J] 2017 Feb 21; Vol. 14 (1), pp. 37. Date of Electronic Publication: 2017 Feb 21. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101231645 Publication Model: Electronic Cited Medium: Internet ISSN: 1743-422X (Electronic) Linking ISSN: 1743422X NLM ISO Abbreviation: Virol J Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : BioMed Central, 2004- |
مواضيع طبية MeSH: | CD8-Positive T-Lymphocytes/*immunology , Dendritic Cells/*immunology , Herpesvirus 1, Human/*immunology , Killer Cells, Natural/*immunology , Macrophages/*immunology , Trigeminal Ganglion/*immunology , Trigeminal Ganglion/*virology, Animals ; Flow Cytometry ; Granzymes/metabolism ; Humans ; Interferon Type I/metabolism ; Interleukin-1beta/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Nitric Oxide Synthase Type II/metabolism ; Toll-Like Receptor 2/deficiency ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 9/deficiency ; Toll-Like Receptor 9/metabolism |
مستخلص: | Background: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1β) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1β production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1. Methods: C57BL/6 (wild type, WT) and TLR2/9 -/- mice were infected by the intranasal route with HSV-1 (1 × 10 6 p.f.u.). Cells were obtained from the TG and spleen tissues and the profile of immune cells was determined by flow cytometry in infected and mock infected WT and knockout mice. The percentage of cells producing iNOS, IL-1β, granzyme B and perforin was also determined by flow cytometry. Chemokine monocyte chemoattractant protein-1 (MCP1) was measured by Cytometric Bead Array (CBA) in the TG, spleen and lung. Expression of type I interferons (IFNs), interleukins (IL) 5 and 10, IL-1β and granzyme B were quantified by real time PCR. Results: The results indicate that dendritic cells (DCs) and monocytes/macrophages (Mo/Mϕ) were the main sources of IL-1β and iNOS, respectively, which, together with type I IFNs, were essential for the immune response against HSV-1. Additionally, we showed that granzyme B produced by CD8 + T and NK lymphocytes and MCP-1 were also important for this immune response. Moreover, our data indicate that the robust production of MCP-1 and granzyme B is either TLR-independent or down regulated by TLRs and occurs in the TG of TLR2/9 -/- infected mice. Conclusion: Taken together, our data provide strong evidence that the responses mediated by DCs, Mo/Mϕ, NK and CD8 + T lymphocytes through IL-1β, iNOS and granzyme B production, respectively, together with the production of type I IFN early in the infection, are crucial to host defense against HSV-1. |
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فهرسة مساهمة: | Keywords: CD8+ T lymphocytes; Dendritic cells; Encephalitis; Herpes simplex virus 1; Innate immunity; Macrophages; Murine model; Neuropathogenesis; TLRs |
المشرفين على المادة: | 0 (Interferon Type I) 0 (Interleukin-1beta) 0 (Tlr2 protein, mouse) 0 (Tlr9 protein, mouse) 0 (Toll-Like Receptor 2) 0 (Toll-Like Receptor 9) EC 1.14.13.39 (Nitric Oxide Synthase Type II) EC 1.14.13.39 (Nos2 protein, mouse) EC 3.4.21.- (Granzymes) EC 3.4.21.- (Gzmb protein, mouse) |
تواريخ الأحداث: | Date Created: 20170223 Date Completed: 20170823 Latest Revision: 20181113 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC5320739 |
DOI: | 10.1186/s12985-017-0692-x |
PMID: | 28222752 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1743-422X |
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DOI: | 10.1186/s12985-017-0692-x |