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The Toll Signaling Pathway Targets the Insulin-like Peptide Dilp6 to Inhibit Growth in Drosophila

Miyuki Suzawa1, Nigel M Muhammad1, Bradley S Joseph1

  • 1Department of Pharmacology, University of Virginia, Charlottesville, VA 22908-0875, USA.

Cell Reports
|August 8, 2019
PubMed

Insights

Chronic infections in children lower insulin-like growth factor 1 (IGF1) and stunt growth. This study reveals Toll signaling suppresses growth by reducing IGF1 levels, linking immunity and growth regulation.

Area of Science:

  • Endocrinology
  • Immunology
  • Developmental Biology

Background:

  • Chronic enteropathogen infection in early childhood is linked to reduced insulin-like growth factor 1 (IGF1) and impaired growth.
  • Pathogen molecules activate host Toll-like receptors, initiating immune responses, but their role in growth inhibition is not fully understood.

Purpose of the Study:

  • To investigate the role of Toll signaling in growth inhibition mediated by infection.
  • To identify specific molecular targets of Toll signaling that affect growth regulation.

Main Methods:

  • Transcriptomic analysis in Drosophila to identify Toll signaling targets.
  • Generation of a tagged allele to measure endogenous Drosophila insulin-like peptide 6 (Dilp6) levels.
  • Genetic manipulation to restore Dilp6 expression in specific tissues.

Main Results:

  • Drosophila insulin-like peptide 6 (Dilp6), an IGF1 ortholog, was identified as a selective target of Toll signaling.
  • Activation of Toll signaling led to a significant reduction in circulating Dilp6 levels.
  • Restoring Dilp6 expression in the fat body rescued growth in animals with active Toll signaling.

Conclusions:

  • Toll signaling suppresses growth by inducing hormone insufficiency, specifically reducing Dilp6 levels.
  • This study establishes a mechanistic link between innate immune signaling and the endocrine regulation of growth.
  • Findings suggest a conserved pathway where immune activation impacts growth through hormonal regulation.

Keywords:
Dilp6DrosophilaTollchronic infectionchronic inflammationenteropathogenfat bodygrowthinnate immunityinsulin signaling

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