The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense

Abstract

Mammals and insects employ similar Rel/NF-κB signaling cascades in their humoral immune responses.The mammalian interleukin-1 type I receptor (IL-1R) is one way of activating this cascade. The Drosophila Toll protein, whose cytoplasmic domain shows striking similarity to that of the IL-1R, acts in the humoral antimicrobial response. Here we demonstrate that a second IL-1R-related Drosophila protein, 18-Wheeler (18W), is a critical component of the humoral immune response. 18-wheeler is expressed in the larval fat body, the primary organ of antimicrobial peptide synthesis. In the absence of the 18W receptor, larvae are more susceptible to bacterial infection. Nuclear translocation of the Rel protein Dorsal-like immunity factor (Dif) is inhibited, though nuclear translocation of another Rel protein, Dorsal, is unaffected. Induction of several antibacterial genes is reduced following infection, relative to wild-type: attacin is reduced by 95%, cecropin by 65% and diptericin by 12%. Finally, 18-wheeler (18w) expression is induced in response to infection and, in addition to the receptor form, four immunespecific transcripts and proteins are produced.

Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants

“…They include the IL-1 receptor accessory protein (IL1AcP) [9] and the putative interferon-␥-inducing factor (also known as IL-1-␥ or IL-18) receptor IL-1 receptor-related protein (IL-1Rrp) [10]. Those belonging to the Toll group have leucine-rich repeats and include another Drosophila protein termed 18-wheeler, which has also been shown to have a role in immunity [11], five human Toll-like receptors (hTLRs), and most interestingly, four plant genes involved in disease resistance [12]. These include N protein from tobacco, which is required for resistance to the pathogen tobacco mosaic virus, and L6 from flax, which confers resistance to flax rust.…”

Synergy and Cross-Tolerance Between Toll-Like Receptor (TLR) 2- and TLR4-Mediated Signaling Pathways

“…Especially, families of Toll-like receptors (TLR) 3 have been shown involved in the recognition of bacterial components. In Drosophila, Toll family proteins specify the innate immune responses to microbial infections; Toll is responsible for the response to fungal infection, whereas 18-wheeler responds to bacterial infection (7,8). Mutations in the Tlr4 gene have been found in LPS-hyporesponsive C3H/HeJ and C57BL/10ScCr mice (9,10).…”

Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity

“…The situation in Drosophila is not nearly so straightforward, however, as both Toll and 18wheeler (18w), which are similar to the mammalian interleukin-1 receptor (IL-1R), also are involved in the antibacterial response (6,7). In addition, the response varies by the individual antibacterial protein gene, with the extent of induction modulated by the type of bacteria (8).…”

“…In addition, the response varies by the individual antibacterial protein gene, with the extent of induction modulated by the type of bacteria (8). Further, some signaling pathway components are also upregulated by infection to some degree, such as Toll, 18w, and the NF B homolog Dorsal-related immunity factor (Dif ) (6,7,9). These observations indicate a highly complex and sophisticated response to immune challenges.…”