Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype

Jessica G. Moreland, Jessica S. Hook, Gail Bailey, Tyler Ulland, William M. Nauseef

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Francisella tularensis, the causative agent of tularemia, is a highly virulent organism, especially when exposure occurs by inhalation. Recent data suggest that Francisella interacts directly with alveolar epithelial cells. Although F. tularensis causes septicemia and can live extracellularly in a murine infection model, there is little information about the role of the vascular endothelium in the host response. We hypothesized that F. tularensis would interact with pulmonary endothelial cells as a prerequisite to the clinically observed recruitment of neutrophils to the lung. Using an in vitro Transwell model system, we studied interactions between F. tularensis live vaccine strain (Ft LVS) and a pulmonary microvascular endothelial cell (PMVEC) monolayer. Organisms invaded the endothelium and were visualized within individual endothelial cells by confocal microscopy. Although these bacteria-endothelial cell interactions did not elicit production of the proinflammatory chemokines, polymorphonuclear leukocytes (PMN) were stimulated to transmigrate across the endothelium in response to Ft LVS. Moreover, transendothelial migration altered the phenotype of recruited PMN; i.e., the capacity of these PMN to activate NADPH oxidase and release elastase in response to subsequent stimulation was reduced compared with PMN that traversed PMVEC in response to Streptococcus pneumoniae. The blunting of PMN responsiveness required PMN transendothelial migration but did not require PMN uptake of Ft LVS, was not dependent on the presence of serum-derived factors, and was not reproduced by Ft LVS-conditioned medium. We speculate that the capacity of Ft LVS-stimulated PMVEC to support transendothelial migration of PMN without triggering release of IL-8 and monocyte chemotactic protein-1 and to suppress the responsiveness of transmigrated PMN to subsequent stimulation could contribute to the dramatic virulence during inhalational challenge with Francisella.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Francisella tularensis
Endothelium
Neutrophils
Phenotype
Endothelial Cells
Transendothelial and Transepithelial Migration
Vaccines
Francisella
Lung
Tularemia
Alveolar Epithelial Cells
Inhalation Exposure
Neutrophil Infiltration
Chemokine CCL2
NADPH Oxidase
Pancreatic Elastase
Vascular Endothelium
Conditioned Culture Medium
Streptococcus pneumoniae
Interleukin-8

Keywords

  • Nadph oxidase
  • Polymorphonuclear leukocyte
  • Pulmonary
  • Tularemia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Francisella tularensis directly interacts with the endothelium and recruits neutrophils with a blunted inflammatory phenotype. / Moreland, Jessica G.; Hook, Jessica S.; Bailey, Gail; Ulland, Tyler; Nauseef, William M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 296, No. 6, 06.2009.

Research output: Contribution to journalArticle

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