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PNAS 106 (49): 20853-20858

Copyright © 2009 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / MEDICAL SCIENCES

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

Justin R. DiAngeloa, Michelle L. Blanda, Shelly Bambinab, Sara Cherryb,1, and Morris J. Birnbauma,1

aThe Institute for Diabetes, Obesity and Metabolism and bDepartment of Microbiology and Penn Genome Frontiers Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Edited by Tom Maniatis, Harvard University, Cambridge, MA, and approved September 24, 2009

Received for publication June 17, 2009.

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.

Key Words: fat body • immunity • Toll • insulin


Author contributions: J.R.D., S.C., and M.J.B. designed research; J.R.D., M.L.B., and S.B. performed research; S.C. contributed new reagents/analytic tools; J.R.D., M.L.B., S.C., and M.J.B. analyzed data; and J.R.D., M.L.B., S.C., and M.J.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0906749106/DCSupplemental.

1To whom correspondence may be addressed. E-mail: birnbaum{at}mail.med.upenn.edu and cherrys{at}mail.med.upenn.edu


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