Francisella tularensis selectively induces proinflammatory changes in endothelial cells.
Naturally acquired infections with Francisella tularensis, the bacterial agent of tularemia, occur infrequently in humans. However, the high infectivity and lethality of the organism in humans raise concerns that it might be exploited as a weapon of bioterrorism. Despite this potential for illicit use, the pathogenesis of tularemia is not well understood. To examine how F. tularensis interacts with cells of its mammalian hosts, we tested the ability of a live vaccine strain (LVS) to induce proinflammatory changes in cultured HUVEC. Living F. tularensis LVS induced HUVEC to express the adhesion molecules VCAM-1 and ICAM-1, but not E-selectin, and to secrete the chemokine CXCL8, but not CCL2. Stimulation of HUVEC by the living bacteria was partially suppressed by polymyxin B, an inhibitor of LPS, but did not require serum, suggesting that F. tularensis LVS does not stimulate endothelium through the serum-dependent pathway that is typically used by LPS from enteric bacteria. In contrast to the living organisms, suspensions of killed F. tularensis LVS acquired the ability to increase endothelial expression of both E-selectin and CCL2. Up-regulation of E-selectin and CCL2 by the killed bacteria was not inhibited by polymyxin B. Exposure of HUVEC to either live or killed F. tularensis LVS for 24 h promoted the transendothelial migration of subsequently added neutrophils. These data indicate that multiple components of F. tularensis LVS induce proinflammatory changes in endothelial cells in an atypical manner that may contribute to the exceptional infectivity and virulence of this pathogen.
Forestal
Colin A
CA
Center for Infectious Diseases, School of Medicine, Stony Brook University, Stony Brook, NY 11794-5120, USA.
Benach
Jorge L
JL
Carbonara
Chateen
C
Italo
Jaime K
JK
Lisinski
Tracy J
TJ
Furie
Martha B
MB
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000032:analysis; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005604:Francisella tularensis / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology; D011112:Polymyxin B / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015164:Vaccines, Inactivated / Q000494:pharmacology; D014774:Virulence / Q000187:drug effects / Q000502:physiology
D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D015815:Cell Adhesion Molecules; D018925:Chemokines; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018836:Inflammation Mediators; D015164:Vaccines, Inactivated; D011112:Polymyxin B