Journal article
Murine FLT3 Ligand-Derived Dendritic Cell-Mediated Early Immune Responses Are Critical To Controlling Cell-Free Human T Cell Leukemia Virus Type 1 Infection
The Journal of immunology (1950), v 186(1), pp 390-402
29 Nov 2010
PMID: 21115731
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human T cell leukemia virus type 1 (HTLV-1) is associated with two immunologically distinct diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia. We observed previously that depletion of dendritic cells (DCs) in CD11c-diphtheria toxin receptor transgenic mice followed by infection with cell-free virus led to greater proviral and Tax mRNA loads and diminished cellular immune response compared with mice infected with cell-associated virus. To understand the significance of these in vivo results and explore the host-pathogen interaction between DCs and cell-free HTLV-1, we used FLT3 ligand-cultured mouse bone marrow-derived DCs (FL-DCs) and chimeric HTLV-1. Phenotypically, the FL-DCs upregulated expression of surface markers (CD80, CD86, and MHC class II) on infection; however, the level of MHC class I remained unchanged. We performed kinetic studies to understand viral entry, proviral integration, and expression of the viral protein Tax. Multiplex cytokine profiling revealed production of an array of proinflammatory cytokines and type 1 IFN (IFN-α) by FL-DCs treated with virus. Virus-matured FL-DCs stimulated proliferation of autologous CD3(+) T cells as shown by intracellular nuclear Ki67 staining and produced IFN-γ when cultured with infected FL-DCs. Gene expression studies using type 1 IFN-specific and DC-specific arrays revealed upregulation of IFN-stimulated genes, most cytokines, and transcription factors, but a distinct downregulation of many chemokines. Overall, these results highlight the critical early responses generated by FL-DCs on challenge with cell-free chimeric HTLV-1.
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Details
- Title
- Murine FLT3 Ligand-Derived Dendritic Cell-Mediated Early Immune Responses Are Critical To Controlling Cell-Free Human T Cell Leukemia Virus Type 1 Infection
- Creators
- Saifur Rahman - Drexel Institute for Biotechnology and Virology ResearchZafar K Khan - Drexel Institute for Biotechnology and Virology ResearchBrian Wigdahl - Department of Microbiology and ImmunologyStephen R Jennings - Department of Microbiology and ImmunologyFrederic Tangy - Génomique Virale et VaccinationPooja Jain - Drexel Institute for Biotechnology and Virology Research
- Publication Details
- The Journal of immunology (1950), v 186(1), pp 390-402
- Publisher
- Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000285688700046
- Scopus ID
- 2-s2.0-79251580628
- Other Identifier
- 991014877884004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology