2. Academic Validation
  3. Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration

Pseudomonas aeruginosa LecB suppresses immune responses by inhibiting transendothelial migration

  • EMBO Rep. 2023 Apr 5;24(4):e55971. doi: 10.15252/embr.202255971.
Janina Sponsel # 1 2 3,  Yubing Guo # 1 2 3,  Lutfir Hamzam 1,  Alice C Lavanant 1,  Annia Pérez-Riverón 1,  Emma Partiot 4 5,  Quentin Muller 1 6,  Julien Rottura 1,  Raphael Gaudin 4 5,  Dirk Hauck 7 8 9,  Alexander Titz 7 8 9,  Vincent Flacher 1,  Winfried Römer 2 3 10,  Christopher G Mueller 1
Affiliations

Affiliations

  • 1 CNRS UPR 3572, IBMC, University of Strasbourg, Strasbourg, France.
  • 2 Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
  • 3 Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • 4 CNRS, Institut de Recherche en Infectiologie de Montpellier (IRIM), Montpellier, France.
  • 5 Université de Montpellier, Montpellier, France.
  • 6 Laboratoire BIOTIS, Inserm U1026, Université de Bordeaux, Bordeaux, France.
  • 7 Chemical Biology of Carbohydrates (CBCH), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, Saarbrücken, Germany.
  • 8 Deutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig, Germany.
  • 9 Department of Chemistry, Saarland University, Saarbrücken, Germany.
  • 10 Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany.
  • # Contributed equally.
PMID: 36856136 DOI: 10.15252/embr.202255971
Abstract

Pseudomonas aeruginosa is a Gram-negative bacterium causing morbidity and mortality in immuno-compromised humans. It produces a lectin, LecB, that is considered a major virulence factor, however, its impact on the immune system remains incompletely understood. Here we show that LecB binds to endothelial cells in human skin and mice and disrupts the transendothelial passage of leukocytes in vitro. It impairs the migration of dendritic cells into the paracortex of lymph nodes leading to a reduced antigen-specific T cell response. Under the effect of the lectin, endothelial cells undergo profound cellular changes resulting in endocytosis and degradation of the junctional protein VE-cadherin, formation of an actin rim, and arrested cell motility. This likely negatively impacts the capacity of endothelial cells to respond to extracellular stimuli and to generate the intercellular gaps for allowing leukocyte diapedesis. A LecB inhibitor can restore dendritic cell migration and T cell activation, underlining the importance of LecB antagonism to reactivate the immune response against P. aeruginosa Infection.

Keywords

bacterial lectin; dendritic cells; lymphatics; migration; skin.

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