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. 2009 Dec 8;106(49):20853-8.
doi: 10.1073/pnas.0906749106. Epub 2009 Oct 27.

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

Justin R DiAngelo  1 , Michelle L Bland, Shelly Bambina, Sara Cherry, Morris J Birnbaum
Affiliations

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

VSports在线直播 - Justin R DiAngelo et al. Proc Natl Acad Sci U S A. .

"VSports手机版" 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 VSports手机版. 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. .

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Conflict of interest statement

The authors declare no conflict of interest.

Figures (VSports手机版)

Fig. 1.
Fig. 1.
Activating the Toll, but not the Imd pathway attenuates insulin signaling. (A) Triglyceride/protein ratios of r4-Gal4>Toll10b, r4-Gal4>RelD, and r4-Gal4>dInRA1325D whole third instar larvae normalized to r4-Gal4>GFP control animals. Each experiment was performed at least three times and values represent the mean ± SEM. *, P < 0.05 compared to GFP, unpaired Student's t-test. (B and C) Immunoblot analyses of phospho-dAkt, total dAkt, and tubulin in fat bodies isolated from 4- to 5-day-old adult females of the following genotypes: (B) yolk-Gal4>GFP, yolk-Gal4>Toll10b, yolk-Gal4>dMyD88, and yolk-Gal4>Dif; (C) yolk-Gal4>GFP, yolk-Gal4>PGRP-LCa, and yolk-Gal4>RelD. Each experiment was performed at least three or four times and representative blots are shown. Phospho-dAkt/total dAkt ratios from the yolk-Gal4>GFP flies from each experiment were set to 1 and each of the experimental genotypes in (B) and (C) was normalized to their respective GFP control. Quantification is shown for three independent experiments. Values represent mean ± SEM. *, P < 0.05 compared to GFP, unpaired Student's t-test.
Fig. 2.
Fig. 2.
Insulin signaling is blunted in response to infection-induced Toll activation. (A and B) Wild-type (w1118) and dMyD88−/−(w1118; dMyD88EP (2)2133) adult females (4 to 7 days old) were injected with insulin alone (−) or insulin and M. luteus (+) and analyzed 10 h postinfection. (A) Immunoblot analyses of phospho-dAkt, total dAkt and tubulin in fat bodies from uninfected (-) and M. luteus infected (+) flies. This experiment was performed five times and representative blots are shown. (B) Triglyceride/protein ratios were measured and normalized to w1118 uninfected controls. Values represent the mean ± SEM. (C and D) Wild-type (yw) adult females (4 to 7 days old) were injected with insulin alone (-) or insulin and B. bassiana fungal spores (+) and analyzed 24 h later. (C) Immunoblot analyses of phospho-dAkt, total dAkt, and tubulin in fat bodies from uninfected (−) and B. bassiana-infected (+) flies. This experiment was performed five times, and a representative blot is shown. Phospho-dAkt/total dAkt ratios from uninfected flies were set to 1 and infected values were normalized to these controls. Quantification is shown for three independent experiments. (D) Triglyceride/protein ratios were measured and normalized to uninfected controls. Values represent the mean ± SEM. *, P < 0.05 by an unpaired Student's t-test.
Fig. 3.
Fig. 3.
Toll signaling inhibits insulin signaling downstream of PI3K. (A and B) Immunoblot analyses of phospho-dAkt, total dAkt, and tubulin in fat bodies isolated from 4- to 5-day-old adult females of the following genotypes: (A) yolk-Gal4>GFP, yolk-Gal4>dInRA1325D, yolk-Gal4>dInRA1325D, Toll10b, and yolk-Gal4>dInRA1325D, Dif; (B) yolk-Gal4>GFP, yolk-Gal4>Dp110CAAX, yolk-Gal4>Dp110CAAX, Toll10b, and yolk-Gal4>Dp110CAAX, Dif. Each set of experiments was performed at least three times, and representative blots are shown. Phospho-dAkt/total dAkt ratios from the yolk-Gal4> dInRA1325D (A) or yolk-Gal4>Dp110CAAX (B) flies from each experiment were set to 1 and each of the other genotypes was normalized to their respective dInRA1325D (A) or Dp110CAAX (B) control. Quantification is shown for three independent experiments. Values represent the mean ± SEM. *, P < 0.05 by an unpaired Student's t-test.
Fig. 4.
Fig. 4.
Subcellular distribution of dFoxo correlates with activity of the insulin signaling pathway. (A) dFoxo (left) and DAPI (right) staining of fat bodies dissected from third instar larvae of the following genotypes: r4-Gal4>GFP (top), r4-Gal4>dInRA1325D, r4-Gal4>Toll10b, and r4-Gal4>Toll10b, dInRA1325D (bottom). (Scale bar, 100 μm.) (B) The ratio of nuclear to cytoplasmic dFoxo was quantified using Image J. Each experimental group (gray bar) is shown compared to its respective r4-Gal4>GFP control (black bar). n = 9–11 fat bodies (GFP), 11 (dInRA1325D), 7 (Toll10b), and 20 (Toll10b, dInRA1325D), Values represent mean ± SEM. *, P < 0.05 vs. control by an unpaired Student's t-test.
Fig. 5.
Fig. 5.
Toll signaling in the fat body nonautonomously inhibits organismal growth. (A and B) Images (left panels) and body weights (right panels) of (A) wandering third instar larvae and (B) 1- to 2-day-old adult females of the following genotypes: r4-Gal4>GFP, r4-Gal4>Toll10b, r4-Gal4>Toll10b, myrAkt, and r4-Gal4>myrAkt. Values are the mean ± SEM. *, P < 0.01 by an unpaired Student's t-test. (C) Immunoblot analyses of phospho-dAkt, total dAkt and tubulin in protein extracts from whole r4-Gal4>GFP and r4-Gal4>Toll10b third instar larvae. This experiment was performed at least three times, and a representative blot is shown. Phospho-dAkt/total dAkt ratios from the r4-Gal4>GFP flies from each experiment were set to 1 and the r4>Toll10b genotype was normalized to the GFP control. Quantification is shown for three independent experiments. Values are the mean ± SEM. *, P < 0.05 by an unpaired Student's t-test. (D) A model illustrating the interaction between fat body Toll and insulin signaling in response to infection to regulate nutrient storage locally and animal growth nonautonomously.
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