The Trends And Clinical Signicance Of Toll-Like Receptors On Dendritic Cells In Peripheral Blood Of Aldut Patients With Severe Burn During The Sub-Acute Phase

ObjectivesAs a serious clinical problem,severe burn injury disturbs the immune system,resulting in progressive suppression of immune response.The dysfunction of dendritic cells(DCs)and the weakening of its antigen devouring ability are the main reason which induces immunosuppression.TLRs are associated with immune system activation,but the effect of TLRs levels on cDCs of severe burn injury patients has not been fully assessed.This research discussed the expression change of Toll-like receptor and the expression tendency of HLA-DR molecule on dendritic cells(DCs)in peripheral blood of patient with major burns,and thus discovered the possibility of DCs dysfunction in septic patients with major burns.MethodsThe prospective case-control study was used to examine the Toll-like receptor expression level on peripheral blood of patient with major burns(burn surface area ≥90%).Healthy volunteers were used as controls.Peripheral blood samples were harvested on 14 days and 28 days later after the burns in patients with major burns(n=10)and control group(n=8).Expression of TLR2,TLR4 and TLR9 on CD11c+ DCs were examined by flow cytometry.PCT,CRP and IL-6 in the peripheral blood were determined by the enzyme linked immunosorbent assay(ELISA).The burn patients were further allocated into survival group and non-survival group to compare the TLR2,TLR4 and TLR9 levels on DCs,as well as DC HLA-DR,peripheral lymphocyte count,serum PCR,CRP and IL-6,so as to evaluate the correlation of the above-mentioned parameters with prognosis.ResultsThe results showed no difference in TBSA,sex,age,or number of operations before the first 14 days(acute-phase)after injury between survivor group and non-survivor group.The HLA-DR on DCs was significantly reduced,suggesting that the antigen presenting function of DCs was compromised.The levels of TLR2,TLR4,and TLR9 in circulating cDCs were significantly and consistently elevated in all patients compared to the age-matched healthy volunteers.The levels of TLR2 and TLR4 on DCs were much higher in survivors than non-survivors.Furthermore,DC TLR2 and TLR4 were upregulated on the 28 th day when compared with those on the 14 th day after burn in survivors,but TLR2 level on the 28 th day was lower than on the 14 th day,and TLR4 levels on the 14 th and 28 th were comparable,suggesting that TLR2 and TLR4 levels were upregulated on DCs after burn,and the compromised upregulation of TLR2 and TLR4 was correlated with poor prognosis.HLA-DR levels on DCs in non-survivors on the 28 th day were lower than those on the 14 th day and than those in survivors.Lymphocyte count in the blood was reduced on the 28 th day compared with the 14 th day,but no significant difference was observed between survivors and non-survivors.Peripheral PCT level was significantly higher in non-survivors than in survivors,but no difference was observed between the PCT levels on the 14 th and 28 th day.ConclusionsHLA-DR level on DCs is reduced in burn patients,while the levels of TLR2,TLR4 and TLR9 are increased.However,the upregulation of TLR2 and TLR4 on DCs is compromised in non-survivors when compared with those in survivors,suggesting that DC dysfunction is present after burn,which is correlated with prognosis of patients.