Identification of recovery mechanisms from infection. Alexander Louie, David Schneider. Microbiology and Immunology, Stanford University, Stanford, CA.

   During an effective immune response, pathogens are eliminated and host physiologies return to baseline. When we discuss infection we do a good job of describing immune effectors but seldom look at recovery. Our goal is to identify the mechanisms that drive recovery from infection. We developed a model system with two criteria. 1) The flies get sick and then recover from infection. 2) We can monitor the effects of microbe levels on pathology. Using this system, we tracked global gene expression changes across the full course of infection in recovering, moribund, and control files. When we plot gene expression levels against microbe load in phase space for all genes, we find that the phase plots group into eight categories: positive and negative linear correlations, clockwise and counter-clockwise loops, positive and negative switches, complex and no change. Phase space analysis puts genes into groups that make biological sense. For example, many of the known immunity genes group together in the positive linear correlations. Phase space is a simple framework for taking apart biological systems. Furthermore, we identified a group of genes that spike as microbe numbers decline. One of these genes is wntD. When we infect and treat wntD mutants they fail to fully recover from infection despite retaining the ability to clear bacteria. wntD expression is required for recovery from infection.