The adipokine NimrodB5 regulates peripheral hematopoiesis in Drosophila

FEBS J. 2020 Aug;287(16):3399-3426. doi: 10.1111/febs.15237. Epub 2020 Feb 17.

Abstract

In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that a secreted protein, NimB5, is produced in the fat body upon nutrient scarcity downstream of metabolic sensors and ecdysone signaling. NimB5 is then secreted and binds to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.

Keywords: Drosophila; Nimrod; growth; metabolism; organ prioritization; peripheral hematopoiesis; trade-off.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / genetics*
  • Adipokines / metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Adhesion / genetics
  • Cell Proliferation / genetics
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Fat Body / metabolism
  • Hematopoiesis / genetics*
  • Hemocytes / cytology
  • Hemocytes / metabolism
  • Larva / cytology
  • Larva / genetics
  • Larva / metabolism
  • Mutation
  • Phagocytosis / genetics
  • Signal Transduction / genetics

Substances

  • Adipokines
  • Drosophila Proteins