Metabolic control of cellular immune-competency by odors in Drosophila

  1. Sukanya Madhwal
  2. Mingyu Shin
  3. Ankita Kapoor
  4. Manisha Goyal
  5. Manish K Joshi
  6. Pirzada Mujeeb Ur Rehman
  7. Kavan Gor
  8. Jiwon Shim  Is a corresponding author
  9. Tina Mukherjee  Is a corresponding author
  1. inStem, India
  2. Hanyang University, Republic of Korea
  3. Institut de Biologie, Aix Marseille Université, CNRS, France
  4. European Molecular Biology Laboratory, Germany

Abstract

Studies in different animal model systems have revealed the impact of odors on immune cells, however, any understanding on why and how odors control cellular immunity remained unclear. We find that Drosophila employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-progenitor cells. We show that neuronally released GABA derived upon olfactory stimulation, is utilized by blood-progenitor cells as a metabolite and through its catabolism, these cells stabilize Sima/HIFα protein. Sima capacitates blood-progenitor cells with the ability to initiate lamellocyte differentiation. This systemic axis becomes relevant for larvae dwelling in wasp-infested environments where chances of infection are high. By co-opting the olfactory route, the pre-conditioned animals elevate their systemic GABA levels leading to the up-regulation of blood-progenitor cell Sima expression. This elevates their immune-potential and primes them to respond rapidly when infected with parasitic wasps. The present work highlights the importance of the olfaction in immunity and shows how odor detection during animal development is utilized to establish a long-range axis in the control of blood-progenitor competency and immune-priming.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5 and Extended Data Figure 1-10.

Article and author information

Author details

  1. Sukanya Madhwal

    Regulation of Cell Fate, inStem, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Mingyu Shin

    Hanyang University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Ankita Kapoor

    Regulation of Cell Fate, inStem, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Manisha Goyal

    Regulation of Cell Fate, inStem, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Manish K Joshi

    Développement de Marseille (IBDM), Institut de Biologie, Aix Marseille Université, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Pirzada Mujeeb Ur Rehman

    Regulation of Cell Fate, inStem, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  7. Kavan Gor

    SCB unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Jiwon Shim

    Hanyang University, Seoul, Republic of Korea
    For correspondence
    jshim@hanyang.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2409-1130
  9. Tina Mukherjee

    Regulation of Cell Fate, inStem, Bangalore, India
    For correspondence
    tinam@instem.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3776-5536

Funding

Department of Biotechnology, Ministry of Science and Technology, India (DBT/PR13446/COE/34/30/2015)

  • Tina Mukherjee

Department of Science and Technology, Ministry of Science and Technology, India (DST/ECR/2015/000390)

  • Tina Mukherjee

Department of Biotechnology, Ministry of Science and Technology, India (Ramalingaswami Fellowship)

  • Tina Mukherjee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bruno Lemaitre, École Polytechnique Fédérale de Lausanne, Switzerland

Version history

  1. Received: June 26, 2020
  2. Accepted: December 28, 2020
  3. Accepted Manuscript published: December 29, 2020 (version 1)
  4. Version of Record published: January 14, 2021 (version 2)

Copyright

© 2020, Madhwal et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,178
    views
  • 591
    downloads
  • 23
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sukanya Madhwal
  2. Mingyu Shin
  3. Ankita Kapoor
  4. Manisha Goyal
  5. Manish K Joshi
  6. Pirzada Mujeeb Ur Rehman
  7. Kavan Gor
  8. Jiwon Shim
  9. Tina Mukherjee
(2020)
Metabolic control of cellular immune-competency by odors in Drosophila
eLife 9:e60376.
https://doi.org/10.7554/eLife.60376

Share this article

https://doi.org/10.7554/eLife.60376

Further reading

    1. Developmental Biology
    Charlotte F Chao, Yanina-Yasmin Pesch ... Elizabeth Rideout
    Research Article

    Drosophila is a powerful model to study how lipids affect spermatogenesis. Yet, the contribution of neutral lipids, a major lipid group which resides in organelles called lipid droplets (LD), to sperm development is largely unknown. Emerging evidence suggests LD are present in the testis and that loss of neutral lipid- and LD-associated genes causes subfertility; however, key regulators of testis neutral lipids and LD remain unclear. Here, we show LD are present in early-stage somatic and germline cells within the Drosophila testis. We identified a role for triglyceride lipase brummer (bmm) in regulating testis LD, and found that whole-body loss of bmm leads to defects in sperm development. Importantly, these represent cell-autonomous roles for bmm in regulating testis LD and spermatogenesis. Because lipidomic analysis of bmm mutants revealed excess triglyceride accumulation, and spermatogenic defects in bmm mutants were rescued by genetically blocking triglyceride synthesis, our data suggest that bmm-mediated regulation of triglyceride influences sperm development. This identifies triglyceride as an important neutral lipid that contributes to Drosophila sperm development, and reveals a key role for bmm in regulating testis triglyceride levels during spermatogenesis.

    1. Developmental Biology
    2. Structural Biology and Molecular Biophysics
    Samuel C Griffiths, Jia Tan ... Hsin-Yi Henry Ho
    Research Article

    The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, Brachydactyly B and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.