Good relations between blood cells of different origins are crucial for an effective immune system
Drosophila lymph gland labelled with antibodies targeting Dot (magenta) and Srp (white) haemocyte markers. PFM (green) indicates the cells that expressed Dot during their development. The nuclei of the cells are marked with DAPI (blue). Credits: Pierre Cattenoz, Claude Delaporte and Angela Giangrande.
July 16, 2018
In fruit flies as in humans, blood cells are produced by successive waves during development. Researchers from Angela Giangrande's team at the IGBMC (CNRS/Inserm /University of Strasbourg) found that the interaction between these two waves is crucial to ensure an effective immune response. An important discovery, knowing that excessive immune system activity can lead to diseases such as cancer. These results are published on July 11, in the journal eLife.
In both Drosophila and humans, blood cells, called haemocytes in the fruitfly, are produced at distinct stages and places. The first wave takes place in the fly embryo to produce the larval hemocytes. The second wave happens at the beginning of metamorphosis, when the larva turns into a pupa: the lymph gland, the organ of the second wave, then bursts to release the haemocytes into the drosophila's blood.
In the larva, parasitoid wasp infestation leads to a strong immune response to neutralize the pathogen. When the wasp lays eggs in the fly larva, the lymph gland bursts earlier to release the haemocytes and kill the wasp eggs. But the mechanisms triggering an adequate immune response are still poorly understood. How does the wasp egg signal at distance to the lymph gland? Are the haemocytes of embryonic origin that patrol the body cavity involved in this process?
In this study, Angela Giangrande's team characterized the molecular pathway that allows first wave hemocytes to send a signal to the lymph gland. They also highlighted the impact of this signalling on the immune response upon infesting larvae that carry defective haemocytes of embryonic origin. This approach allowed them to show that a communication mechanism is set up in the embryo during the development of the first wave hemocytes. A gene called Gcm, involved in the development of these haemocytes, also regulates the implementation of several elements of this mechanism. If Gcm expression is altered, the development of the first wave hemocytes is altered. The hemocytes then send a stronger signal to the lymph gland, leading to an exacerbated immune response. Since Gcm is only expressed in embryogenesis, this molecule must imprint the hemocytes issued from the first wave and hence control their behavior at the larval stage.
These results thus made it possible to characterize a communication mechanism between the first and the second waves of hematopoiesis while stressing the importance of early development on the late functions of the immune system. In addition, they also help us understanding how the immune system is built and functions. If this mechanism is maintained in humans, this study will also help understanding how fetal stress can have a negative long-term impact after birth and lead to immune diseases.
This study was funded by the ANR, the Regional Cancer League, the Strasbourg Hospitals and the ARC.