Abstract：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 production and expression of phosphorylated protein kinase-like endoplasmic reticulum kinase (PERK) and activator 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 patients 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 tuberculosis 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 related to ER phosphorylation modification may drive the immunosuppressive/antiproliferative T cell response in tuberculosis patients.
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2024, Vol. 30 
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