Innate immunity in fruit flies: a textbook example of genomic recycling

Abstract

Drosophila serve as a wonderful model for studying aspects of innate immunity, i.e. the physical, cellular, and molecular features that provide the first lines of defense against infections in flies and man

Figure 1. Innate Immune Responses of Drosophila

(A) Posterior region of a third instar larva showing the cuticle and the trachea. These structures provide a physical barrier against infections. Cellular immune reactions consist of phagocytosis, encapsulation, and melanization. (B) A dead and melanized crystal cell phagocytosed by a plasmatocyte. (C) Encapsulation of an egg of a Drosophila parasite. The parasite is a wasp that normally infects larvae. Cells surrounding the egg are lamellocytes. The cells and the egg are stained with a fluorescent nuclear stain. (D) Clot formation occurs during wound healing. (E) Crystal cells in contact with the larval cuticle. The contents of the crystal cells are melanized. Melanization occurs in response to intruding pathogens or parasites and is also observed during wound healing. (F) Humoral immune reaction. The expression of antimicrobial peptides in the larval fat body is induced by microbes. Cells of the fat body appear green due to the presence of a transgene encoding the green fluorescent protein, under the control of the drosomycin promoter. The drosomycin promoter is activated in response to fungal infections and is under the control of the Toll pathway (see Figure 2). Antimicrobial peptides are released from the fat body into the hemolymph. This response is therefore systemic. A similar antimicrobial gene activation response can occur locally in specific body parts such as the trachea or the gut (not shown).

Figure 2. Molecular Components of the Toll and Imd Pathways Involved in Drosophila Immunity

Toll is activated by the processed Spätzle (left). Toll activation leads to intracellular signaling via cytoplasmic proteins Tube and Pelle, leading to the degradation of Cactus and nuclear localization of NF-κB proteins Dorsal and Dif. These transcription factors bind to promoters of target genes, such as drosomycin, activating their transcription. The NF-κB protein for the Imd pathway, Relish, activates diptericin transcription. The signaling events resulting in Dorsal/Dif/Relish activation in the fly are “recycled” in mammals in the activation of mammalian NF-κB. See reviews and De Gregorio et al. (2002) for more details.