Mapping immune responses one cell at a time

Cell Systems: Single cell analysis of diverse pathogen responses defines a molecular roadmap for generating antigen-specific immunity

New research tracking the journey of pathogens through the body has highlighted differences in the immune system’s response to allergens and bacterial or fungal infections that could offer potential new avenues for treatment.

The Health Research Council-funded research, by New Zealand’s Malaghan Institute of Medical Research and the Weizmann Institute of Science in Israel, looks at what happens to pathogens (such as parasitic worm allergens, bacteria or fungi) as they are received, sorted, recognised and processed by the various cells within the immune response.

Published in the prestigious scientific journal Cell Systems, the paper ‘Single cell analysis of diverse pathogen responses defines a molecular roadmap for generating antigen-specific immunity,’ uses single-cell transcriptomics to show that while on the outside an immune response to a bacterial antigen or parasite allergen may look similar, the steps these different pathogens go through to get there are very different.

“We were delighted to collaborate with the group of Ido Amit at the Weizmann, who is a pioneer in this field” says Professor Ronchese, who led the Malaghan Institute’s research team. “By following the individual cells that take up the different pathogens you can really see the make-up of the immune response. Already by 24 hours you can see the differences between the response to an allergen compared to the response to a bacterial or fungal infection.”

Specifically, Prof Ronchese explains that this research has allowed them to identify the different types of immune cells called in to deal with different types of responses, an important step in understanding how the immune system deals with different kinds of threats.

“The immune system is made up of thousands of different cells and many cell types,” says Prof Ronchese. “In reality, only about one percent of those cells are actually involved in taking up and dealing with allergens during the early days of an immune response. By looking at all the cells one by one, we can see where the action is. Now we can focus on the key players and ask exactly what they do, how does it impact the immune response, and what can we do to change it.”

Single-cell “transcriptomics” are revolutionising understanding of biology due to their power to provide exhaustive information of complex biological systems at a single cell level. For this reason, transcriptomics has been voted “2018 breakthrough of the year” by the top scientific journal Science. Transcriptomics enable scientists to track complex, overarching events or responses that may be too complex to be studied piece by piece.

By pinpointing which immune cells are responsible for starting an allergic reaction, Prof Ronchese hopes that this research will pave the way for future work interrupting these cells, preventing allergies from developing in the first place.

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