Requirement of miR155 for NK cell and CD8+ T cell responses against viral infection (115.7)

Abstract Natural killer (NK) cells and CD8+ T cells function similarly in the recognition and destruction of host cells infected with pathogens. Although microRNAs (miRs) are critical for NK and T cell development and function, the role of specific miRs remain to be investigated. We discovered that miR155 is induced in activated NK cells during mouse cytomegalovirus (MCMV) infection. Using mice containing a targeted deletion of miR155, we determined that miR155 is indispensible for MCMV-specific NK cell expansion and generation of long-lived NK cells. Although miR155-deficient NK cells do not have any defects in basal NK cell homeostasis or function, they exhibit severely impaired effector and memory cell numbers in both lymphoid and non-lymphoid tissues following viral infection. Furthermore, miR155-deficient CD8+ T cells are similarly compromised in their ability to undergo clonal expansion and survive following MCMV infection, together resulting in substantially diminished memory cell numbers. Thus, miR155 is essential for the generation of protective effector and memory NK and CD8+ T cells during viral infection.