Of Mice and Monocytes: Anthrax and the Host Genomic Response

Here we investigate anthrax invasion across
epithelial monolayers, human monocyte genomic
responses, and mouse genomic responses in spleens,
lungs, and livers. Differences in response to
toxigenic, and non-toxigenic anthrax strains are
discussed and described. Interestingly, epithelial
monolayers containing human THP-1 cells expressing a
macrophage phenotype showed increased permeability
and bacterial invasion than with just epithelial
cells alone. In fact, apoptotic pathways and
mediators in THP-1 cells appear to be repressed upon
challenge by toxigenic strains, and more activated
in challenges by non-toxigenic strains. We observed
an upregulation of the apoptotic inhibitor cFLAR
during toxigenic infection of human monocytes, and a
phenotypical delay in apoptosis for the toxigenic
strain-challenged cells. In the mouse model, CASH,
the mouse homologue of the human cFLAR, is induced
and the apoptotic response is suppressed in liver,
an organ with a large proportion of monocyte-derived
Kupffer cells. These results indicate a role for the
delay of cFLAR-mediated apoptosis as a key virulence
factor in the disease.

Autorentext

Chris Bradburne was born in the northern Shenandoah Valley of
Virginia and raised on a small farm there. His journey in
science has taken him from deep-sea hydrothermal vents, to
astrobiology, to infectious disease. Since 2007, he has been a
National Research Council Associate at the Naval Research
Laboratory in Washington, D.C.

Klappentext

Here we investigate anthrax invasion across
epithelial monolayers, human monocyte genomic
responses, and mouse genomic responses in spleens,
lungs, and livers. Differences in response to
toxigenic, and non-toxigenic anthrax strains are
discussed and described. Interestingly, epithelial
monolayers containing human THP-1 cells expressing a
macrophage phenotype showed increased permeability
and bacterial invasion than with just epithelial
cells alone. In fact, apoptotic pathways and
mediators in THP-1 cells appear to be repressed upon
challenge by toxigenic strains, and more activated
in challenges by non-toxigenic strains. We observed
an upregulation of the apoptotic inhibitor cFLAR
during toxigenic infection of human monocytes, and a
phenotypical delay in apoptosis for the toxigenic
strain-challenged cells. In the mouse model, CASH,
the mouse homologue of the human cFLAR, is induced
and the apoptotic response is suppressed in liver,
an organ with a large proportion of monocyte-derived
Kupffer cells. These results indicate a role for the
delay of cFLAR-mediated apoptosis as a key virulence
factor in the disease.