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

Download

index.pdf

Date

2017-02-07

Author

Gucluler, Gozde
Adiguzel, Emre
Gungor, Bilgi
Kahraman, Tamer
Gürsel, Mayda
Yilmaz, Bilge
GÜRSEL, İHSAN

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

227
views

98
downloads

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 IFN alpha. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4(+) T-cell dependent IFN. 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 IFN gamma 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.

Subject Keywords

General Biochemistry, Genetics and Molecular Biology, General Agricultural and Biological Sciences, General Medicine

URI

https://hdl.handle.net/11511/47722

Journal

PLOS ONE

DOI

https://doi.org/10.1371/journal.pone.0171003

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2, -2B and SPANX-B, during Mesenchymal-to-Epithelial Transition Yilmaz-Ozcan, Sinem; Sade, Asli; Kucukkaraduman, Baris; Kaygusuz, Yasemin; Senses, Kerem Mert; Banerjee, Sreeparna; GÜRE, ALİ OSMAY (Public Library of Science (PLoS), 2014-09-17) Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated duri...
Ca2+ binding induced sequential allosteric activation of sortase A: An example for ion-triggered conformational selection Ugur, Iike; Schatte, Martin; Marıon, Antoıne; Glaser, Manuel; Boenitz-Dulat, Mara; Antes, Iris (Public Library of Science (PLoS), 2018-10-15) The allosteric activation of the intrinsically disordered enzyme Staphylococcus aureus sortase A is initiated via binding of a Ca2+ ion. Although Ca2+ binding was shown to initiate structural changes inducing disorder-to-order transitions, the details of the allosteric activation mechanism remain elusive. We performed long-term molecular dynamics simulations of sortase A without (3 simulations of 1.6 mu s) and with bound Ca2+ (simulations of 1.6 mu s, 1.8 mu s, and 2.5 mu s). Our results show that Ca2+ bind...
Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects Binder, Julia; Carta, Silvia; Carvalho, Julene S.; Kalafat, Erkan; Khalil, Asma; Thilaganathan, Basky (Public Library of Science (PLoS), 2020-2-5) Aims Fetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies. Methods This...
Target-specific delivery of doxorubicin to human glioblastoma cell line via ssDNA aptamer BAYRAÇ, TAHİR; Akca, Oya Ercan; Eyidogan, Fusun Inci; Öktem, Hüseyin Avni (Springer Science and Business Media LLC, 2018-03-01) Targeted drug delivery approaches have been implementing significant therapeutic gain for cancer treatment since last decades. Aptamers are one of the mostly used and highly selective targeting agents for cancer cells. Herein, we address a nano-sized targeted drug delivery approach adorned with A-172 glioblastoma cell-line-specific single stranded DNA (ssDNA) aptamer in which the chemotherapeutic agent Doxorubicin (DOX) had been conjugated. DNA aptamer, GMT-3, was previously selected for specific recognitio...
Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke CAN DEMİRDÖĞEN, BİRSEN; Sahin, Esra; Ozcelik, Aysun Turkanoglu; Bek, Semai; Demirkaya, Seref; Adalı, Orhan (Springer Science and Business Media LLC, 2012-12-01) Atherosclerosis, a major cause of ischemic stroke, may be associated with variability of triglyceride (TG) levels. Apolipoprotein A5 (APOA5) genetic polymorphisms are associated with altered TG levels. The objective of this study was to investigate the coding region polymorphisms S19W (rs3135506) and G185C (rs2075291) and the promoter region polymorphism -1131T > C (rs662799) of the APOA5 gene as risk factors for ischemic stroke in Turkish population. Study group consisted of 272 ischemic stroke patients an...

Citation Formats

G. Gucluler et al., “Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction,” PLOS ONE, pp. 0–0, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/47722.