ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1624014
This article is part of the Research TopicSystems Immunology and Translational Research in Infectious DiseasesView all 7 articles
Plasma polymeric immunoglobulin receptor exacerbates lung injury in Klebsiella pneumoniae-induced pneumosepsis
Provisionally accepted
Shuaiwei Wang1Hao Fu1,2Xiaoqing Li1,3Hongrui Xu1Yu Bai1Wenjun Jiang1Xiaozhe Cheng1Na Chen1,4
Yijie Zhang1,5
Wei Li1*- 1Sepsis Laboratory, The Second College of Clinical Medicine, Henan University, Kaifeng, China
- 2Department of Endocrine and Metabolic Diseases, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, China
- 3Clinical Laboratory, The First People's Hospital, Shangqiu, China
- 4Department of Pulmonary and Critical Care Medicine, The Second College of Clinical Medicine, Henan University, Kaifeng, China
- 5Department of Clinical Medicine, Luohe Medical College, Luohe, China
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Background: 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 is 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).Results: 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 Klebsiella pneumoniae (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 absentce 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.Conclusions: 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.
Keywords: Sepsis, Polymeric immunoglobulin receptor, Klebsiella pneumoniae, Alveolar type 2 epithelial cells, pyroptosis, caspase-11
Received: 06 May 2025; Accepted: 13 Jun 2025.
Copyright: © 2025 Wang, Fu, Li, Xu, Bai, Jiang, Cheng, Chen, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Li, Sepsis Laboratory, The Second College of Clinical Medicine, Henan University, Kaifeng, China
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