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 macro-phage 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.