Research Of Toll-like Receptors And T Lymphocyte Subsets In The Pathogenesis Of Herpes Zoster

Objective Herpes zoster(HZ)is an infectious skin disease caused by the reactivation of varicella zoster virus(VZV)in the spinal dorsal root ganglion.About 20% healthy adults and 50% immunodeficiency population can occur HZ,and blisters and neuralgia as its main clinical manifestation.After the skin lesions disappeared,patients are accompanied with irreversible postherpetic neuralgia.Immunocompromised patients are prone to develop system involvement,manifested as pneumonia,hepatitis,encephalomyelitis,vascular disease,which seriously affect the physical and mental health and quality of life of patients.At present,the pathogenesis of HZ is mainly related to immune functions,but its pathogenesis is not yet clear.Therefore,it is of great significance to explore the pathogenesis of HZ,especially in the immune mechanism.Innate immune system recognizing pathogen associated molecular patterns(PAMPs)by pattern recognition receptors(PRR),is the body's first line of defense to against invading pathogens.Toll like receptor(TLR)is the major PRRs in innate immune system.Innate immune response is induced after recognition and ligand-binding of TLRs.Some studies found that the partial TLR m RNA expression becomes increased when VZV primary infects host,which activating signal transduction factor,inducing the production of inflammatory cytokines,indirectly activating T lymphocyte to mediate cellular immune response,but the expression of TLR in the pathogenesis of HZ are not clear.Different lymphocyte subsets are not only closely link to each other but also restrain to each other in their respective differentiation and regulation of immune system function,which remains the body balance.Some scholars have found that the number and function of CD8+T and CD4+T and their cell subsets have changed since the activation of VZV,but the role and mechanism of T lymphocyte and its subsets in the pathogenesis of HZ is not clear.In this study,the expression of TLR2,4,7,9m RNA and protein in peripheral blood mononuclear cell(PBMC)and the constituent ratio of T lymphocytes,helper T cell subsets(Th1,Th2,Th17 cells)and regulatory T cells(Treg)and the ratio of CD4+T/CD8+T,Th1/Th2,Th17/Treg and related cytokines were detected to investigate the role of TLRs and cellular immunity in the pathogenesis of HZ,providing the theoretical basis for the further treatment of HZ.Method Collection the peripheral blood of 31 patients with HZ and 32 healthy people of control group.PBMC from 31 HZ patients and 32 healthy people were isolated by density gradient centrifugation on Ficoll-Paque,the expression of TLR 2,TLR4,TLR7 and TLR9 protein was detected by flow-cytometric analysis.Total RNA was extracted from the rest of PBMC with Trizol reagent,to detect the expression of TLR2,TLR4,TLR7 and TLR9 m RNA in PBMC by real-time quantitative reverse transcription polymerase chain reaction(RT-PCR).The constituent ratio of T lymphocytes and helper T cell subsets(Th1,Th2,Th17,Treg cells)and the ratio of CD4+T/CD8+T,Th1/Th2,Th17/Treg of peripheral blood of subjects were detected by flow cytometric analysis.The lever of IL-2,IL-4,IL-6,IL-10,IL-17 A and IFN-? in serum of patients and control group were determined by Cytometric Bead Array(CBA).Result The results showed that,as compared to normal control,the expression of TLR2,TLR4,TLR7 and TLR9 m RNA in PBMC of patients with HZ significantly increased(t=2.253,2.945,3.042,2.629;P <0.05),but the expression of TLR4 and TLR7 protein were significantly higher(t=2.334,4.543;P <0.05);the expression of TLR2 and TLR9 protein were significantly lower(t=5.840,3.328;P <0.05)in HZ than those in normal controls.The results showed that the ratio of CD3+CD8+T,Th1,Treg cells of patients with HZ significantly increased as compared with control group,while the ratio of CD3+CD4+,Th2 cells decreased significantly in patients with HZ;there was a tendency to reduce of the ratio of CD4+T/CD8+T,Th1/Th2,Th17/Treg cells in patients with HZ(t=3.14,2.48,2.07;P <0.05);there was no difference in the ratio of Th2.The lever of IL-6,IL-10 and IFN-? in herpes zoster patients serum increased dramatically compared with that in control group(t=2.87,3.51,2.36;P <0.05),and there was no difference in the lever of IL-2,IL-4,IL-17 A.Conclusion These results indicate that TLR2,TLR4,TLR7 and TLR9 may play an important roles in the pathogenesis of HZ,and the imbalance of T lymphocyte and its subsets in patients with HZ may participate in the pathogenesis of HZ.