Constitutive Immune Activity Promotes Tumorigenesis in Drosophila Intestinal Progenitor Cells.

Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells.

Independent Proteolytic Activities Control the Stability and Size of Drosophila Inhibitor of Apoptosis 2 Protein.

The Drosophila immune deficiency pathway defends many bacterial pathogens and bears striking molecular similarities to the mammalian tumor necrosis factor signal transduction pathway. Orthologous inhibitors of apoptosis ubiquitin ligases act at a proximal stage of both responses to coordinate the assembly of signal transduction platforms that shape host immune responses. Despite the importance of inhibitor of apoptosis proteins within evolutionarily conserved innate immune responses, we know relatively little about the cellular machinery that controls inhibitor of apoptosis activity.

The protein Dredd is an essential component of the c-Jun N-terminal kinase pathway in the Drosophila immune response.

The Drosophila immune deficiency (IMD) pathway mobilizes c-Jun N-terminal kinase (JNK), caspase, and nuclear factor-κB (NF-κB) modules to counter infection with gram-negative bacteria. Dredd is an essential caspase in the IMD pathway, and it is widely established that NF-κB activation depends on Dredd. More recent cell culture studies suggested a role for Dredd in the activation of dJNK (Drosophila JNK).

Dnr1-dependent regulation of the Drosophila immune deficiency signaling pathway.

Innate immunity is a critical metazoan defense strategy that rapidly detects and neutralizes invading microbes. As the signaling pathways that drive innate immune responses are evolutionarily conserved, there is considerable interest in the characterization of innate immune signaling in genetically tractable models, such as Drosophila melanogaster. Drosophila responds to detection of diamonopimelic-type microbial peptidoglycan through activation of the immune deficiency (Imd) pathway, a signaling pathway with numerous similarities to the mammalian pro-inflammatory TNF pathway.