A Specific Primed Immune Response in Drosophila Is Dependent on Phagocytes

Abstract

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.

Author Summary

Due to the common practice of vaccination and prominence of AIDS, people are already aware of the distinction between adaptive and innate immunity without realizing it. All organisms have an innate immune response, but only vertebrates possess T cells and the ability to produce antibodies. It has been a long-standing assumption that invertebrate immune systems are not adaptive and respond identically to multiple challenges. In this study, we demonstrate that the fly innate immune response adapts to repeated challenges; flies preinoculated with dead Streptococcus pneumoniae are protected against a second, otherwise-lethal dose. Although the underlying mechanisms are likely to be very different, this primed response is reminiscent to vaccine-induced protection in that it exhibits coarse specificity (dead S. pneumoniae only protects against itself), persists for the life of the fly and is dependent on phagocytic cells. This result prompts the obvious question of whether the innate immune system of vertebrates shares a similar biology. Such a finding is of particular interest since immunocompromised individuals only possess an innate immune system.