MicroRNA influence on host response to Francisella infection

Abstract

The gram‐negative bacterium Francisella tularensis has the ability to subvert host immune response and is the causative agent of the disease tularemia. Previous work has identified the roles of PI3K, Akt and SHIP in modulating host resistance to Francisella. However, the mechanisms of F. tularensis host cell subversion are still poorly understood.microRNAs (miRs) have emerged as an important regulatory system in the modulation of host innate immune response. Since miRs have the potential to regulate key immune functions such as NFkappaB activity and TLR signaling, we examined whether they played a role during Francisella infection. We performed a miR array analysis of human myeloid cells infected with Francisella. This led to the identification of several miRs that were significantly up‐ or down‐regulated by Francisella. We subsequently verified many of these changes using real‐time RT‐PCR in both human and murine cells. Currently we are examining the roles of these miRs by identifying their targets and by modulating miR activity itself during Francisella infection. Interestingly, our data so far indicate that SHIP and PI3K/Akt regulate the expression of several miRs. As specific miR targets are identified within the context of Francisella infection, it is likely that novel therapeutic targets will be found, and that the mechanisms of Francisella host cell subversion will be further elucidated.