Using Drosophila as a model, the systemic immune response has been the paradigm of invertebrate responses to microbial infection. This body of research has demonstrated that this response is not adaptive, as seen in invertebrate immunity, but is adapted to specific pathogens through the regulation of the Toll and Imd pathways. The specificity of this response is based on the use of a large array of effectors, although the mechanisms these effectors employ to control microbes remain unclear.
Recent studies focusing on the local response to pathogens are starting to reveal the emerging complexity of the epithelial immune response. Further study of epithelial infections will assist in identifying features specific to local immunity and clarify the growing link between the stress and immune responses. Additionally, increased understanding of the role of microbiota in the development and function of the innate immune response will help elucidate the complex mechanisms underlying gut homeostasis.
Finally, emerging studies in Drosophila support the consideration of the innate immune response as a holistic process. The interplay between different tissues and the integration of these responses probably contributes to each host-microbe interaction (Lemaitre and Hoffmann, 2007; Shirasu-Hiza and Schneider, 2007). Thus, signalling between the local and systemic response, while not required in every interaction, may dictate whether microbial infection leads to tolerance, resolution, or host lethality. The role of this signalling and its in-depth characterization are some of the current challenges facing the field of innate immunity.
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