Study Finds How Individual Macrophages React To Different Stimuli

Researchers from Yale School of Engineering and Applied Sciences have used single-cell RNA sequencing in order to get a closer look on how individual macrophages react to different stimuli. 

So, what are these macrophages? They are immune cells that both fight infections and fix the damage they cause. They are often placed into two categories
1. Those that increase inflammation (known as “M1”) to attack
2. Those that decrease inflammation to begin the healing process (“M2”).

The research found that while these cells tend to be multitaskers, some are more inclined toward responding to certain cues than others. The M1-M2 paradigm has helped the study in understanding how the innate immune responses.

There has been a long suspicion in flexibility among macrophages in vivo than this two-category system suggests—that is, a cell can be both an attacker or healer depending on the situation.

The question here is what do individual macrophages do when confronted with M1, M2 cues at the same time in a controlled environment. 

Kathryn Miller-Jensen, associate professor of biomedical engineering and molecular, cellular & developmental biology, answered by saying that it wasn’t yet explored and they too tried with single-cell sequencing itself. This helped them get a detailed picture of macrophages.

They found a great deal of variability, including a subset of cells that seem to respond to only one cue or the other for certain key functions like secretion.

Jensen added that the stimuli are environmental cues, and the team is thinking about the idea that there might be some difference in regulatory networks inside the cells, which allows few of them to respond more strongly to one cue versus another.

It’s an important step toward a better understanding of the different macrophages.

This could give an insight into how the macrophages exist in such different states in a tumour. Detailed knowledge about this can help regulate them in a more proper way.

The researchers note that the diverse responses to opposing cues may allow macrophages to more readily adapt to changing environments, and to quickly transition from attack mode to focusing on tissue repair.

Jensen said, “They might need to respond to a lot of cues at the same time, so a few of the macrophages might be primed to respond and be the attackers”. “So when they see both of those cues at the same time, it’s important to have at least some of those cells to secrete what needs to be secreted—but maybe not all of those cells, because some may need to do something else.”

Jensen also said that this single-cell RNA sequencing technology, and the single-cell secretion device (invented by Prof. Rong Fan, also in biomedical engineering) played a critical part in making the groundbreaking observations.

Journal Reference:
Andrés R. Muñoz-Rojas et al. Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells, Nature Communications (2021). DOI: 10.1038/s41467-020-20540-2

Press Release: Yale University