Wang Shuaiwei, Fu Hao, Li Xiaoqing, Xu Hongrui, Bai Yu, Jiang Wenjun, Cheng Xiaozhe, Chen Na, Zhang Yijie, Li Wei
Sepsis Laboratory, Center for Translational Medicine, The Second College of Clinical Medicine, Henan University, Kaifeng, Henan, China.
Department of Endocrine and Metabolic Diseases, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, Guangdong, China.
Front Immunol. 2025 Jun 26;16:1624014. doi: 10.3389/fimmu.2025.1624014. eCollection 2025.
Polymeric immunoglobulin receptors (pIgR) may enhance mucosal immunity or worsen an infection through transcytosis of polymeric immunoglobulins or infectious pathogens. The function of plasma pIgR in infections remains unknown.
The association of plasma pIgR with the occurrence and prognosis of sepsis was investigated using human plasma. The role and underlying mechanisms of plasma pIgR were investigated in mouse models of sepsis and primary alveolar type 2 epithelial cells (AT2).
Quantitative proteomic and ELISA analysis revealed a significant association between plasma pIgR and the prognosis of patients of pneumonia-induced sepsis. Intravenous administrations of recombinant pIgR (r_pIgR) increased the mortality in mouse models of (KP)-induced pneumosepsis (KPS) and polymicrobial sepsis. r_pIgR also increased the injury score, caspase-11 and GSDMD-NT in the lungs of KPS mice. pIgR-neutralizing antibody (pIgR_Ab) exhibited opposite effects on animal survival in both sepsis models and on the injury score, caspase-11 and GSDMD-NT. Notably, r_pIgR did not affect the survival of Caspase-11-deficient KPS mice. pIgR immunoreactivity was absent in alveoli in normal mice, but emerged exclusively in AT2 in KPS mice. r_pIgR significantly reduced the level of biomarkers for AT2, but not AT1, whereas pIgR_Ab increased the level of AT2 biomarkers. In primary mouse AT2, heat-inactivated KP induced a marked increase in GSDMD-NT only in the presence of both r_pIgR and IgM.
This study demonstrates that plasma pIgR is a potential prognostic marker for sepsis, and likely contributes to AT2 pyroptosis and sepsis lethality through interaction with IgM, indicating a broad pro-pathogenic role of plasma pIgR in infectious diseases.
聚合免疫球蛋白受体（pIgR）可通过聚合免疫球蛋白或传染性病原体的转胞吞作用增强黏膜免疫或加重感染。血浆pIgR在感染中的功能尚不清楚。
使用人血浆研究血浆pIgR与脓毒症发生和预后的关联。在脓毒症小鼠模型和原代肺泡II型上皮细胞（AT2）中研究血浆pIgR的作用及其潜在机制。
定量蛋白质组学和酶联免疫吸附测定分析显示血浆pIgR与肺炎诱发脓毒症患者的预后之间存在显著关联。静脉注射重组pIgR（r_pIgR）会增加肺炎克雷伯菌（KP）诱发的肺炎脓毒症（KPS）和多重微生物脓毒症小鼠模型的死亡率。r_pIgR还增加了KPS小鼠肺部的损伤评分、半胱天冬酶-11和Gasdermin D N端结构域（GSDMD-NT）。pIgR中和抗体（pIgR_Ab）在两种脓毒症模型中对动物存活率以及损伤评分、半胱天冬酶-11和GSDMD-NT均表现出相反的作用。值得注意的是，r_pIgR不影响半胱天冬酶-11缺陷型KPS小鼠的存活率。正常小鼠肺泡中不存在pIgR免疫反应性，但仅在KPS小鼠的AT2中出现。r_pIgR显著降低了AT2生物标志物的水平，但对AT1生物标志物水平无影响，而pIgR_Ab则增加了AT2生物标志物的水平。在原代小鼠AT2中，热灭活的KP仅在同时存在r_pIgR和IgM的情况下才会导致GSDMD-NT显著增加。
本研究表明血浆pIgR是脓毒症的潜在预后标志物，可能通过与IgM相互作用导致AT2细胞焦亡和脓毒症致死率增加，表明血浆pIgR在传染病中具有广泛的促致病作用。
