Francisella novicida Infection Modulates the miRNA Content in Exosomes Released from Murine Macrophages




Mackie, Ryan

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Macrophages are the first line of innate defense for many diseases. Intercellular communication between infected macrophages and uninfected bystander cells of the host may be mediated via exosomes, small (50-100 nm) vesicles released from a variety of mammalian cell types shown to play a role in cell-cell communication and priming of the immune system. The contents of these extracellular vesicles include microRNA (miRNA) species that may represent a new mode of systemic signal transmission between either proximal or distal cells. We hypothesized that intracellular pathogens such as Francisella may affect the amount and type of RNA species that are predominantly packaged into exosomes compared to naïve, uninfected cells. We purified and characterized exosomes from F. novicida infected and uninfected J774A.1 murine macrophage cells. We analyzed the miRNA content of exosomes from infected cells by RNA sequencing and found differential miRNA expression contained therein. We demonstrate here that two murine miRNAs, miR-155-5p and miR-146a-5p, are up-regulated in infected cells and in the exosomes released from these cells. We also demonstrate that delivery of exogenous miR-155-5p to naïve J774A.1 cells can alter their responsiveness to F. novicida infection and alter the cellular level of miR-146a-5p. Thus, exosomes from Francisella infected cells could deliver miRNAs to naïve bystander cells and alter their susceptibility to pathogen infection, and thus potentially modulate the host response to infection.



Francisella, Micro RNA, Exosomes, Macrophages