Molecular mechanism of immune evasion by Francisella tularensis through the induction of prostaglandin E2 from infected cells. (129.14)

Abstract Francisella tularensis is a highly virulent gram negative bacterium. Because of the low infectious dose, we investigated possible mechanisms of immune evasion. We have previously demonstrated Francisella tularensis ability to induce the production of prostaglandin E2 (PGE2) from infected cells. PGE2 is a potent regulator of immune responses. Our objective is to identify the F. tularensis product responsible for the induction of PGE2 production. We screened a Francisella transposon mutant library and identified 20 candidate genes. These candidate genes were then expressed in ANA-1s, a macrophage cell line. The expression of open reading frame FTL0119 in ANA-1's caused the macrophage cell line to produce more PGE2 than ANA-1s transfected with other candidate genes. We then generated nonpolar markerless deletions of the FTL0119 ORF in F. tularensis Live Vaccine Strain. As expected, mutant F. tularensis LVS failed to induce the production of PGE2 from bone marrow-derived macrophages. Thus we have identified a gene, FTL0119, which is likely to be directly responsible for the induction of PGE2 from F. tularensis infected macrophages and a contributor to immune evasion.