A human macrophage – hepatocyte co-culture model for comparative studies of infection and replication of Francisella tularensis LVS strain and subspecies holarctica and mediasiaticaReportar como inadecuado




A human macrophage – hepatocyte co-culture model for comparative studies of infection and replication of Francisella tularensis LVS strain and subspecies holarctica and mediasiatica - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Microbiology

, 16:2

First Online: 06 January 2016Received: 27 August 2015Accepted: 29 December 2015DOI: 10.1186-s12866-015-0621-3

Cite this article as: Rennert, K., Otto, P., Funke, H. et al. BMC Microbiol 2016 16: 2. doi:10.1186-s12866-015-0621-3

Abstract

BackgroundFrancisella tularensis, a gram-negative bacterium replicates intracellularly within macrophages and efficiently evades the innate immune response. It is able to infect and replicate within Kupffer cells, specialized tissue macrophages of the liver, and to modulate the immune response upon infection to its own advantage. Studies on Francisella tularensis liver infection were mostly performed in animal models and difficult to extrapolate to the human situation, since human infections and clinical observations are rare.

ResultsUsing a human co-culture model of macrophages and hepatocytes we investigated the course of infection of three Francisella tularensis strains subspecies holarctica – wildtype and live vaccine strain, and mediasiatica - wildtype and analyzed the immune response triggered upon infection. We observed that hepatocytes support the intracellular replication of Franciscella species in macrophages accompanied by a specific immune response inducing TNFα, IL-1β, IL-6 and fractalkine CX3CL1 secretion and the induction of apoptosis.

ConclusionsWe could demonstrate that this human macrophage - hepatocyte co-culture model reflects strain-specific virulence of Francisella tularensis. We developed a suitable tool for more detailed in vitro studies on the immune response upon liver cell infection by F. tularensis.

KeywordsFrancisella tularensis Human macrophage Hepatocyte Co-culture Liver AbbreviationsCHACysteine heart agar

CFUColony forming unit

CX3CL1Fractalkine

DMEMDulbecco’s modified eagle medium

ECMEndothelial cell medium

FKNFractalkine

F. tularensisFrancisella tularensis

GM-CSFGranulocyte-macrophage colony stimulating factor

ILInterleukin

LPSLipopolysaccharide

LVSLive vaccine strain

MOIMultiplicity of infection

Pen-Strp.Penicillin-Streptomycin

RTRoom temperature

spp.Subspecies

WBCWhite blood cell

v-vVolume-Volume

Electronic supplementary materialThe online version of this article doi:10.1186-s12866-015-0621-3 contains supplementary material, which is available to authorized users.

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Autor: Knut Rennert - Peter Otto - Harald Funke - Otmar Huber - Herbert Tomaso - Alexander S. Mosig

Fuente: https://link.springer.com/







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