Impact of Chronic Infection on Resistance and Tolerance to Secondary Infection in Drosophila melanogaster

Prior exposure to a pathogen can greatly influence the outcome of a secondary infection, and although invertebrates lack classically defined adaptive immunity, their immune response is still influenced by prior immune challenges. While the strength and specificity of such immune priming depends highly on the host organism and infecting microbe, chronic bacterial infection of the fruit fly Drosophila melanogaster with species isolated from wild-caught fruit flies provides broad nonspecific protection against a later secondary bacterial infection. To determine how chronic infection influences progression of secondary infection, we specifically tested how chronic infection with Serratia marcescens and Enterococcus faecalis impacted both resistance and tolerance to a secondary infection with an unrelated bacterium, Providencia rettgeri, by simultaneously tracking survival and bacterial load postinfection across a range of infectious doses. We found that these chronic infections increased both tolerance and resistance to P. rettgeri. Further investigation of S. marcescens chronic infection also revealed robust protection against the highly virulent Providencia sneebia, and that protection was dependent on the initial infectious dose for S. marcescens with protective doses corresponding with significantly increased diptericin expression. While the increased expression of this antimicrobial peptide gene likely explains the increased resistance, increased tolerance is likely due to other alterations in organismal physiology, such as increased negative regulation of immunity or tolerance of ER stress. These findings provide a foundation for future studies on how chronic infection influences tolerance to secondary infection.