A Short Receptor Downregulates JAK/STAT Signalling to Control the Drosophila Cellular Immune Response

David S Schneider,Joanna Krzemień,Michèle Crozatier,Virginie Daburon,Anne Braun,Alain Vincent,Henri-Marc Bourbon,Rami Makki,Jean-Michel Ubeda,Rui Zhou,Marie Meister,Delphine Pennetier

doi:10.1371/journal.pbio.1000441

Abstract

Author SummaryA specific microenvironment termed the “niche” supports long term maintenance of hematopoietic stem cells in vertebrates. A small group of specialised cells called the posterior signalling center (PSC) controls hemocyte (blood cell) homeostasis in the Drosophila larval hematopoietic tissue and thus fulfills a similar function to the vertebrate niche. The PSC acts at a distance to maintain JAK/STAT signalling in hematopoietic progenitors (prohemocytes), thereby ensuring their multipotent character. We report here that a short cytokine receptor encoded by CG14225/latran is required to extinguish JAK/STAT signalling in prohemocytes and thereby ensures their mass differentiation into lamellocytes, an immune cell type required to fight specific threats such as wasp parasitism. Domeless, a related receptor in Drosophila, was previously the only known cytokine receptor that signals through the JAK/STAT pathway. We show that Latran lacks the intracellular domains required for signal transduction and acts instead by antagonizing the function of Domeless in a dose-dependent manner. The role of Drosophila Latran in the repression of JAK/STAT signalling under specific immune conditions raises the question of whether short, nonsignalling receptors that antagonize full-length receptors could also control specific aspects of vertebrate immunity.

Highlights

The innate immune response–the synthesis of antimicrobial peptides and mobilisation of dedicated immune cells–confers a broad protection against pathogens to all multicellular organisms
The posterior signalling centre (PSC) acts at a distance to maintain JAK/STAT signalling in hematopoietic progenitors, thereby ensuring their multipotent character
We report here that a short cytokine receptor encoded by CG14225/ latran is required to extinguish JAK/STAT signalling in prohemocytes and thereby ensures their mass differentiation into lamellocytes, an immune cell type required to fight specific threats such as wasp parasitism

Summary

Introduction

The innate immune response–the synthesis of antimicrobial peptides and mobilisation of dedicated immune cells–confers a broad protection against pathogens to all multicellular organisms. Drosophila has become a model for studying the role of hematopoietic (blood) cells and the evolution of cellular immunity (reviews by [1,2]). Drosophila hematopoiesis occurs in two waves during development [3]. A first population of hemocytes is specified in the embryo and gives rise to plasmatocytes involved in phagocytosis and crystal cells required for melanisation [4]. A second wave of plasmatocyte and crystal cell production occurs at the end of larval development. Larval hematopoiesis can give rise to a third cell type, the lamellocytes, which are devoted to the encapsulation of foreign bodies too large to be phagocytosed. Larval hematopoiesis takes place in a specialised organ, the lymph gland (LG), which forms during embryogenesis and grows during larval development.

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