Immune-metabolic interaction in <i>Drosophila</i>

Dionne, Marc S.

doi:10.4161/fly.28113

Cited by 27 publications

(25 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we showed that TEP2 and TEP4 are involved in regulating the activation of immune signaling pathways in Photorhabdus-infected flies (11,35). Several studies have linked immune signaling pathway activity to metabolic status in Drosophila in the context of infection (7). For example, insulin signaling and triglyceride synthesis were attenuated in Toll gain-of-function mutants, but not in Imd mutants, in the absence of infection (46).…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

et al. 2018

View full text Add to dashboard Cite

is an outstanding model for studying host antipathogen defense. Although substantial progress has been made in understanding how metabolism and immunity are interrelated in flies, little information has been obtained on the molecular players that regulate metabolism and inflammation in during pathogenic infection. Recently, we reported that the inactivation of thioester-containing protein 2 () and promotes survival and decreases the bacterial burden in flies upon infection with the virulent pathogens and Here, we investigated physiological and pathological defects in mutant flies in response to challenge. We find that and loss-of-function mutant flies contain increased levels of carbohydrates and triglycerides in the presence or absence of infection. We also report that infection leads to higher levels of nitric oxide and reduced transcript levels of the apical caspase-encoding gene in and mutants. We show that and are upregulated mainly in the fat body rather than the gut in -infected wild-type flies and that mutants contain decreased numbers of bacteria in both tissue types. We propose that the inactivation of or in adult flies results in lower levels of inflammation and increased energy reserves in response to , which could confer a survival-protective effect during the initial hours of infection.

show abstract

Section: Discussionmentioning

confidence: 96%

“…Infection also induces stress signaling cascades, resulting in the synthesis of nitric oxide (6). To accomplish these immune functions, Drosophila relies on its stored reservoirs of energy (7). Metabolism and immunity share a complex relationship depending on the nature of the pathogen that the fly encounters.…”

mentioning

confidence: 99%

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The importance of the systemic regulation of energy is demonstrated by examples of certain infections leading to depletion of energy reserves (wasting) and eventually death of the organism [ 15 , 19 ]. Despite the importance of the systemic regulation of energy, we have only fragmentary knowledge about the molecular mechanisms involved in the regulation of energy during immune response at the organismal level and about the communication between different parts of the organism mediating the shift of energy from storage and growth towards immunity [ 12 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

et al. 2015

View full text Add to dashboard Cite

Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues.

show abstract

“…Insulindeficient Drosophila and insulin-resistant Drosophila exhibit reduced size, developmental delay, and hyperglycemia and serve as models of type 1 and type 2 diabetes, respectively (12)(13)(14). In Drosophila, as in other organisms, a complex relationship between insulin signaling and the immune response exists (15)(16)(17)(18)(19)(20). In some settings, increased immunity and increased insulin signaling promote healing: the immune response contributes to the repair of epidermal DNA damage in an InR-dependent manner (21), and epidermal wound healing requires InR (22).…”

mentioning

confidence: 99%

A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance

Musselman

Fink

Grant

et al. 2018

Molecular and Cellular Biology

View full text Add to dashboard Cite

Systemic and tissue-specific insulin resistance have been described in , and are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body using loss- and gain-of-function. When expression of the sole Insulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, RNA-seq studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathways and identify new targets of insulin signaling that could serve as potential drug targets to treat type 2 diabetes.

show abstract

Immune-metabolic interaction in Drosophila

Cited by 27 publications

References 40 publications

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and Inflammation Response in Drosophila

Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance

Contact Info

Product

Resources

About