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Drosophila melanogaster,  like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming  Drosophila  with a sublethal dose of  Streptococcus pneumoniae  protects against an otherwise-lethal second challenge of  S. pneumoniae.  This protective effect exhibits coarse specificity for  S. pneumoniae  and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by  Beauveria bassiana,  a natural fly pathogen. To characterize this primed response, we focused on  S. pneumoniae –induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

A Specific Primed Immune Response in Drosophila Is Dependent on Phagocytes