Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction
Public Library of Science
1 - 13
Item Usage Stats
MetadataShow full item record
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.
Pathogen associated molecular pattern
Toll like receptor 7
Toll like receptor 9
Antigen presenting cell
Peripheral blood mononuclear cell
Plasmacytoid dendritic cell
Spinal cord injury
Published Version (Please cite this version)http://dx.doi.org/10.1371/journal.pone.0171003
Showing items related by title, author, creator and subject.
Cekic, C.; Linden, J. (Nature Publishing Group, 2016)Cellular stress or apoptosis triggers the release of ATP, ADP and other nucleotides into the extracellular space. Extracellular nucleotides function as autocrine and paracrine signalling molecules by activating cell-surface ...
Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy Spisek, R.; Kukreja, A.; Chen, L. -C.; Matthews, P.; Mazumder, A.; Vesole, D.; Jagannath, S.; Zebroski, H. A.; Simpson, A. J. G.; Ritter, G.; Durie, B.; Crowley, J.; Shaughnessy, Jr. J.D.; Scanlan, M. J.; Gure, A. O.; Barlogie, B.; Dhodapkar, M. V. (Rockefeller University Press, 2007)Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of ...
Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG Yildiz, S.; Alpdundar, E.; Gungor, B.; Kahraman, T.; Bayyurt, B.; Gursel, I.; Gursel, M. (Wiley - V C H Verlag GmbH & Co. KGaA, 2015)Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized ...