A bacterial YopJ-family acetyltransferasesuppresseshost immune response by Ne-acetylation of JAK1
A common host response to pathogen infection involves the production of robust interferons or proinflammatory cytokines to activate the JAK-STAT pathway, thereby limiting pathogen replication. The bacterial pathogen Legionella pneumophila creates an intracellular niche and evades host immunity utilizing a cohort of effectors by diverse biochemical activities, thereby permissive for its intracellular replication. However, roles of the JAK-STAT pathway during bacterial infection remain elusive. Here, we identify for the first time that L.pneumophila acetyltransferase effector Lem17 acts as a negative regulator of the JAK-STAT signaling. Lem17 directly interacts with JAK1 through a JAK1-binding Box1-like motif, preventing its recruitment by cytokine receptors. As a YopJ-family acetyltransferase, Lem17 catalyzes Ne-lysine acetylation of JAK1 and impairs its kinase activity, thereby disrupting JAK1-mediated signaling transduction. Our findings provide new insights into the mechanism by which L. pneumophila subverts host immunity through acetylation and underscore the role of the JAK-STAT pathway against bacterial infection. Overall design: RNA-sequencing (RNA-seq) analysis on IFN-ß-primed HeLa cells ectopically expressing Lem17 or an empty vector.