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      Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

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      Author
      Gucluler, G.
      Adiguzel, E.
      Gungor, B.
      Kahraman, T.
      Gursel, M.
      Yilmaz, B.
      Gursel, I.
      Date
      2017
      Source Title
      PLoS ONE
      Print ISSN
      1932-6203
      Publisher
      Public Library of Science
      Volume
      12
      Issue
      2
      Pages
      1 - 13
      Language
      English
      Type
      Article
      Item Usage Stats
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      80
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      Abstract
      Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. © 2017 Gucluler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
      Keywords
      Alpha interferon
      Corticosteroid
      Ionomycin
      Lipopolysaccharide
      Methylprednisolone
      Pathogen associated molecular pattern
      Toll like receptor 7
      Toll like receptor 9
      Biological marker
      Cytokine
      Ligand
      Adaptive immunity
      Antigen presenting cell
      B lymphocyte
      Cell stimulation
      Clinical article
      Controlled study
      Cytokine release
      Immune dysregulation
      Immunocompetent cell
      Immunostimulation
      Infection sensitivity
      Innate immunity
      Monocyte
      Peripheral blood mononuclear cell
      Plasmacytoid dendritic cell
      Spinal cord injury
      T lymphocyte
      Lymphocyte activation
      Metabolism
      Mononuclear cell
      pathology
      Biomarkers
      Chronic disease
      Cross-sectional studies
      Cytokines
      Leukocyte count
      Ligands
      Lymphocyte activation
      Permalink
      http://hdl.handle.net/11693/37020
      Published Version (Please cite this version)
      http://dx.doi.org/10.1371/journal.pone.0171003
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