Of Mice and Monocytes: Anthrax and the Host Genomic Response - Paperback

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.