Host defenses to Rickettsia rickettsii infection contribute to increased microvascular permeability in human cerebral endothelial cells

Michael E. Woods, Juan P. Olano

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Rickettsiae are arthropod-borne intracellular bacterial pathogens that primarily infect the microvascular endothelium leading to systemic spread of the organisms and the major pathophysiological effect, increased microvascular permeability, and edema in vital organs such as the lung and brain. Much work has been done on mechanisms of immunity to rickettsiae, as well as the responses of endothelial cells to rickettsial invasion. However, to date, no one has described the mechanisms of increased microvascular permeability during acute rickettsiosis. We sought to establish an in vitro model of human endothelial-target rickettsial infection using the etiological agent of Rocky Mountain spotted fever, Rickettsia rickettsii, and human cerebral microvascular endothelial cells. Endothelial cells infected with R. rickettsii exhibited a dose-dependent decrease in trans-endothelial electrical resistance, which translates into increased monolayer permeability. Additionally, we showed that the addition of pro-inflammatory stimuli essential to rickettsial immunity dramatically enhanced this effect. This increase in permeability correlates with dissociation of adherens junctions between endothelial cells and is not dependent on the presence of nitric oxide. Taken together, these results demonstrate for the first time that increased microvascular permeability associated with rickettsial infection is partly attributable to intracellular rickettsiae and partly attributable to the immune defenses that have evolved to protect the host from rickettsial spread.

Original languageEnglish (US)
Pages (from-to)174-185
Number of pages12
JournalJournal of Clinical Immunology
Volume28
Issue number2
DOIs
StatePublished - Mar 1 2008

Keywords

  • Bacterial infection
  • Cytokines
  • Microvascular permeability
  • Nitric oxide
  • Rickettsiae

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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