The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling

Abstract

Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection against a foreign organism is energetically costly, creating the need to reallocate substrates from nonessential functions, such as growth and nutrient storage. However, the mechanism by which infection or inflammation leads to a reduction in energy utilization by these dispensable processes is not well understood. Here, we demonstrate that activation of the Toll signaling pathway selectively in the fat body, the major immune and lipid storage organ of the fruit fly, Drosophila melanogaster, leads to both induction of immunity and reallocation of resources. Toll signaling in the fat body suppresses insulin signaling both within these cells and non-autonomously throughout the organism, leading to a decrease in both nutrient stores and growth. These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection.fat body ͉ immunity ͉ Toll ͉ insulin

The Innate Immune Response Transcription Factor Relish Is Necessary for Neurodegeneration in aDrosophilaModel of Ataxia-Telangiectasia

“…To determine whether Relish activation in glial cells is sufficient to produce these outcomes, we characterized Repo-GAL4,UAS-RelD flies that overexpressed the constitutively active Relish NF-kB motif only in glial cells (Sepp et al 2001;DiAngelo et al 2009). To control for effects due to protein overexpression, we characterized Repo-GAL4,UAS-GFP (Green fluorescent protein) flies.…”

“…Activated Relish translocates to the nucleus and promotes the transcription of IIR genes, including AMP genes. In support of this mechanism, overexpression of the Relish NF-kB motif in the fat body, a major immune-responsive tissue, is sufficient to stimulate Relish target gene expression (DiAngelo et al 2009;Wiklund et al 2009). Finally, NF-kB-independent pathways activate portions of the IIR, but these pathways are primarily involved in tissue-specific constitutive expression of IIR genes rather than inducible pathogenmediated expression (Han et al 2004;Ryu et al 2004;Peng et al 2005;Senger et al 2006;Tzou et al 2010).…”

Integrating nutrition and immunology: A new frontier

“…Molecular studies of the interactions between metabolic pathways and innate immunity have provided a new understanding of the interactions between nutrition and immune defense in insects (Castillo et al, 2011;DiAngelo et al, 2009). Mutations of genes in the insulin signaling pathway have considerable effects on immunity.…”

IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity

“…Because immune cells lack significant glycogen stores, the metabolic demands of these activated cells are primarily met by rapid uptake of extracellular glucose (5,6). Thus, in the context of bacterial infection, the inhibition of insulin signaling by inflammatory molecules might be an adaptive response that redirects glucose from storage to host defense (7,8). Although this nutrient reallocation strategy is protective during bacterial infection, it becomes maladaptive in the setting of obesity, resulting in insulin resistance and type 2 diabetes (7,(9)(10)(11).…”