Differential Activation of the NF-κB-like Factors Relish and Dif in Drosophila melanogaster by Fungi and Gram-positive Bacteria

Abstract

The current model of immune activation in bacteria. Various fungi stimulated antimicrobial peptides through at least two different pathways requiringRelish and/or Dif. Induction of Attacin A by Geotrichum candidum required Relish, whereas activation by Beauvaria bassiana required Dif, suggesting that the Drosophila immune system can distinguish between at least these two fungi. We conclude that the Drosophila immune system is more complex than the current model. We propose a new model to account for this immune system complexity, incorporating distinct pattern recognition receptors of the Drosophila immune system, which can distinguish between various fungi and G ؉ bacteria, thereby leading to selective induction of antimicrobial peptides via differential activation of Relish and Dif.

Host Immune Response and Differential Survival of the Sexes in Drosophila

“…Although classically the two pathways have been considered to be independent, various reports have increasingly shown interactions, for example in activation of antimicrobial protein genes. 4,21 More recently, synergy between the Toll and Imd pathways in activating an immune response has been directly addressed and synergy demonstrated through cooperation of the different NFkB-related transcription factors of the two pathways. 22 We used natural infection with B. bassiana, which means that first contact with the fungus occurs with the surface epithelia of the fly.…”

Nuclear factor-kappa B pathways in Drosophila

“…In any event, activation of the Imd pathway results in C-terminal partial proteolysis of Relish, much like what occurs with p100 in vertebrates, leading to the nuclear translocation of the RH domain part of Relish. Relish controls the expression of the antimicrobial peptides Attacin, Cecropin and Diptericin (Dushay et al, 1996;Stoven et al, 2003;Hedengren-Olcott et al, 2004;Imler and Bulet, 2005). Exactly how proteolytically cleaved Relish activates target genes is not known; for example, whether there is a Bcl-3 homolog in flies that acts as a co-activator for processed Relish is not known.…”

“…This receptor adaptor complex relays the signal to the Cactus-NF-kB protein (Dif and/or Dorsal) complex (Ip et al, 1993;Manfruelli et al, 1999;Meng et al, 1999). Dif is the predominant transactivator in the antifungal and anti-Gram-positive bacterial infections (Rutschmann et al, 2000a;Hedengren-Olcott et al, 2004). Dorsal functions redundantly with Dif in larval immune response, but Dorsal does not function in the adult immune response.…”

Microarray analyses reveal distinct roles for Rel proteins in the Drosophila immune response

“…The imd pathway regulates Relish activation in a similar way: signal-dependent cleavage of the inhibitory ankyrin repeat domain of Relish leads to release of the Rel domain responsible for transcription [8][9][10]. During an immune response, differential Toll and imd pathway activation of the three NF-κB proteins is believed to cause different transcriptional outcomes [11]. In vitro evidence demonstrates heterodimerization and homodimerization of the three Rel proteins can create transcription factors with different target specificities [12].…”