Correlation Study of Endoplasmic Reticulum Phosphorylation Modification and Immune Response in Pulmonary Tuberculosis Infection
Objective:To observe the correlation between phosphorylation of endoplasmic reticulum(ER)and immune response after pulmonary tuberculosis infection.Methods:In this observational study,we recruited adult tuberculosis patients(n=19)who were treated in our hospital from January 2021 to June 2023 and family contacts(healthy contacts)who had no symptoms of tuberculosis(n=20).Blood samples were collected from all patients before treatment,and the characteristics of specific T cell response,cytokine pro-duction and expression of phosphorylated protein kinase-like endoplasmic reticulum kinase(PERK)and acti-vator of transcription 3(STAT3)of Mycobacterium tuberculosis were analyzed.Results:Compared with healthy contacts,the levels of IL-17 and IL-22 in whole blood samples stimulated by PPD in tuberculosis pa-tients decreased significantly(P<0.05),and the levels of IL-6 and IL-10 increased significantly(P<0.05).Compared with healthy contacts,the spontaneous concentrations of IL-10,IL-6 and IFN-γ in tubercu-losis patients were higher(P<0.05).In the absence of IL-6 stimulation in vitro,the level of PERK in CD4+ T cells of tuberculosis patients was significantly higher than that of healthy contacts(P<0.001).Adding IL-6 led to a significant increase in the level of PERK in CD4+ T cells of healthy contacts compared with those without IL-6 stimulation in vitro(P<0.01).Compared with healthy contacts,CD4+ T cells of tuberculosis patients had higher expression of STAT3 protein(P<0.05).In all donors and tuberculosis patients,there was a significant positive correlation between the expression of PERK and STAT3 in CD4+ T cells(rho=0.571,0.503,all P<0.05).The ratio of CD40L/IL-2 co-expressing T cells and CD40L/IFN-γ co-expressing T cells was negatively correlated with STAT3 expression only in tuberculosis patients(rho =-0.481,-0.705,P= 0.032,<0.001).Conclusion:This study provides evidence that the PERK/STAT3 signaling pathway relat-ed to ER phosphorylation modification may drive the immunosuppressive/antiproliferative T cell response in tu-berculosis patients.
Endoplasmic reticulumT cellsPulmonary tuberculosisPhosphorylated protein kinase-like endoplasmic reticulum kinaseImmune response
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