The Gram-negative intracellular pathogen Francisella tularensis is known for its ability to dampen host immune responses. We recently performed a microarray analysis comparing human monocyte responses to the highly virulent F. tularensis tularensis Schu S4 strain (F.t.) versus the less virulent F. tularensis novicida (F.n.).(1) Many groups of genes were affected, including those involved with autophagy and with the regulation of autophagy. Here, we discuss the implications in the context of Francisella virulence and host cell response, then conclude with potential future experiments.