Involvement of bronchial epithelium in sepsis-induced immunosuppression - 17/02/23

Doi : 10.1016/j.rmr.2022.11.045 
J. Malherbe 1, A. Friol 1, C. Rousseau 1, C. Dauriat 1, E. Péju 1, 2, J.F. Llitjos 1, L. Boulant 1, C. Martin 1, 3, B. Chassaing 1, P.R. Burgel 1, 3, F. Pène 1, 2, M.Z. Ladjemi 1, 2,
1 Institut Cochin, Inserm U1016, CNRS UMR8104, université Paris Cité, Paris, France 
2 Service de médecine intensive et réanimation, hôpital Cochin, Assistance publique–Hôpitaux de Paris, Centre et université Paris Cité, Paris, France 
3 Service de pneumologie et centre de référence maladies rares coordonnateur Mucoviscidose, hôpital Cochin, Assistance publique–Hôpitaux de Paris, Paris, France 

Corresponding author.



Post septic hosts show altered lung immunity with increased susceptibility to bacterial pneumonia. The role of sepsis-induced dysregulation of airway epithelium immune function has not yet been investigated. Moreover, the microbiota is emerging as an essential factor of regulation of mucosal immunity. We hypothesized here that sepsis-induced alterations in airway epithelium contribute to defective lung defense towards secondary bacterial pneumonia. Hence, we examined morphological and functional alterations of airway epithelium induced by non-pulmonary polymicrobial sepsis, together with a focus on the intestinal and lung microbiota composition.


C57BL/6J female mice were used for the experiments. Mice were subjected to double-hit infectious insults through polymicrobial peritonitis induced by cecal ligation and puncture (CLP) or control sham surgery, followed eight days after by intratracheal instillation of 4106 colony forming units (CFU) of Pseudomonas aeruginosa (PAO1). Morphology and functions of airway epithelial cells were studied by immunohistochemistry and flow cytometry on days 3 and 7 after surgery, prior to any secondary bacterial challenge. Gut (faeces) and lung microbiota diversity was studied by 16S RNA sequencing.


As compared to sham-operated controls, post-septic mice exhibited increased mortality towards secondary P. aeruginosa pneumonia, associated with increased systemic spread of the pathogen. Post-septic mice exhibited reduced thickness of bronchial epithelium on day 3, associated with decreased proliferative capacity (as assessed by Ki67 immunostaining). However, bronchial epithelium became hypertrophied in post-septic mice at delayed time point (day 7), thereby suggesting altered tissue repair. Tissue barrier functions were also altered as suggested by reduced epithelial expression of tight and adherens junctions (as assessed by Zonula occludens 1 and E-cadherin immunostainings). Increased expression of immune checkpoint inhibitors (e.g. Programed Death Ligands PD-L1 and PD-L2) and Toll-like receptors 2 and 5 was also observed in bronchial and alveolar epithelial cells from post-septic mice. Finally, we observed gut and lung dysbiosis in post-septic mice as compared to sham-operated mice.


Our results suggest that non-pulmonary sepsis may modulate the main functions of airway epithelial cells and may thereby impact remotely on lung immune defense towards secondary bacterial pneumonia. How this may affect mucosal immunity, possibly in relation with local dysbiosis, should now be investigated.

El texto completo de este artículo está disponible en PDF.


© 2022  Publicado por Elsevier Masson SAS.

    Exportación citas

  • Fichero

  • Contenido

Vol 40 - N° 2

P. 131-132 - février 2023 Regresar al número
Artículo precedente Artículo precedente
  • Staphylococcus aureus is capable of inducing a neutrophilic inflammation in a surgical mouse model of CRS, in a more prominent way than Pseudomonas aeruginosa or Streptococcus pneumoniae
  • A. Sánchez-Montalvo, A. Ziani-Zeryouh, M. Lecocq, C. Bouzin, C. Pilette, V. Hox
| Artículo siguiente Artículo siguiente
  • Développement d’une approche antisens pour activer le canal alternatif TMEM16a chez les patients atteints de mucoviscidose
  • C. Mitri, N. Rousselet, C. Corvol, O. Tabary

¿Ya suscrito a @@106933@@ revista ?