Plasma polymeric immunoglobulin receptor exacerbates lung injury in Klebsiella pneumoniae-induced pneumosepsis

To screen proteins associated with sepsis lethality, we selected 12 pairs of plasma samples from 12 sepsis patients, each pair corresponding to the moderate and moribund phases of the same patient. We detected 15 different polymeric immunoglobulin receptor (pIgR)-unique peptides, all of which are located in the extracellular domain of pIgR through tandem-mass tagged mass spectrometry, suggesting the presence of secreted pIgR in the plasma. Importantly, the quantity of pIgR peptides was 42.8% higher in the moribund than moderate plasma. Further analysis showed that the level of plasma pIgR is a potential prognostic marker of sepsis. Using animal models of Klebsiella pneumoniae-induced pneumosepsis and polymicrobial sepsis, we found that plasma pIgR increases sepsis lethality. The deleterious effect of plasma pIgR is likely mediated by caspase-11-dependent pyroptosis of alveolar type 2 epithelial cells in mice of pneumosepsis. The activation of pyroptosis of type 2 epithelial cells by Klebsiella pneumoniae requires the presence of both pIgR and IgM. These findings demonstrate that plasma pIgR plays a detrimental role in sepsis, an infection-induced organ failure syndrome that claims millions of lives annually worldwide.