Of Mice and Monocytes

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.