Shuttling: A New Kind of Pathogen Transfer Between Immune Cells
While studying the early stages of fungal infection, researchers from the Lieschke group at ARMI and their collaborators have made a fascinating discovery: a new type of pathogen transfer between immune cells. After a passionate 10 years of observation and experimentation, this work has now been published in a – quite literally – beautiful paper, entitled, “β-glucan–dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment” in the journal PLoS Biology.
“This work contributes to understanding fungal mechanisms of immune evasion, drug resistance, and host interactions with infection which might help develop new drugs for the patients who need it the most.” – Professor Graham Lieschke
What makes this study so elegant in both scientific design and aesthetics is the sophisticated biological tools and top-of-the-line visualisation techniques the group used. High-resolution 4-dimensional confocal microscopy in live zebrafish enabled researchers to watch what individual immune cells (neutrophils and macrophages) do when they encounter a fungal pathogen in a whole organism setting. The zebrafish neutrophils and macrophages, the injected fungal spores, as well as a host of other components were labelled with different colours, producing hours of colourful videos.
It was in these videos that the team saw something new – a neutrophil transferring a fungal spore to a macrophage through direct cell-to-cell contact, and both cells ‘walking away’ from the interaction alive and well. This wasn’t an accident or a false positive. This happened again and again. The immune cells sent out cell protrusions as if shaking hands, then the neutrophil passed one or multiple fungal spores to the macrophage, a process the group termed ‘shuttling’. This only happened in the first few hours of infection. Because it only happened with fungal spores and not inert beads of the same size, it was possible to identify a fungal structural chemical that provides a signal that triggers shuttling.
So what does it all mean? It’s not clear yet whether this shuttling serves to benefit the host or the fungal pathogen. But we do know that the first few hours of fungal infection are crucial for infection establishment so shuttling may play an important role in the outcome of infection. Could it be that neutrophils shuttle fungal spores to macrophages because macrophages are better at engaging an adaptive immune response? Or could it be that shuttling is fungal-driven, because the macrophage environment is less hostile than the neutrophil one? Using the tools and techniques this project has developed and refined, including zebrafish models and microscopy protocols, these questions are the next to be tackled.
This project has been a decade-long commitment of the team, led by Professor Graham Lieschke. Professor Lieschke, who also works as a clinician and sees the problems that lung fungal infections can cause in his cancer patients, says. “This work contributes to understanding fungal mechanisms of immune evasion, drug resistance, and host interactions with infection which might help develop new drugs for the patients who need it the most”. With the discovery of fungal spore shuttling comes a deeper understanding of host-pathogen interactions and the potential for new anti-fungal therapies to be developed. Congratulations to Professor Lieschke and all his co-authors at ARMI and around the world.
More information
Click here to read the publication: Pazhakh V, Ellett F, Croker BA, O’Donnell JA, Pase L, Schulze KE, et al. β-glucan–dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment. PLoS Biol 2019;17(9):e3000113.
The Lieschke Group studies the haemopoietic system (blood production) and leukocytes (white blood cells). For more information on Professor Graham Lieschke and his group at ARMI, please visit the Lieschke Group page. You can contact Professor Graham Lieschke via graham.lieschke@monash.edu.