How blood cells remote-controle your brain

This is a time of great uncertainty. Fresh from a global health crisis, we are constantly confronted with harsh realities. Crashing markets, spiralling conflicts, natural disasters and political discourse are all around us without us really looking for them. Not surprisingly, many of us experience feelings of anxiety and emotional turmoil, unable to break out of the constant fight or flight mode. Do we prevail or do we surrender?

Image by Peretz Partensky via Wikimedia Commons (accessed under CC BY-SA 2.0)

I would argue that almost everyone is familiar with this concept of facing our fears or running away from them. But why do we choose one over the other? And why are boys, at least as described by the Masculine Honour Ideology (MHI) [1], more likely to face a threat while girls seem to be more likely to run away from it? The answer may, at least in part, be in the blood. Researchers at Chongqing Medical University in China have shown that blood cells can influence your behaviour in threatening situations, and that there is a clear difference between male and female mice when it comes to threat avoidance [2].

Male mice are thrill seekers

In a series of tests, the researcher wanted to better understand the behaviour of laboratory mice in the context of social threats, i.e. the perceived threat from another individual. To do this, the mice first had to learn that other mice could mean danger. Normally, mice are social animals that actively seek out other individuals, even those that are unfamiliar to them. In the learning phase, this natural tendency was coupled with an unpleasant, but overall harmless, electric shock to make the experimental mice think that approaching a conspecific was associated with potential harm. When the mice were later presented with an unfamiliar individual, it was not surprising that they avoided approaching, at least as long as the tested animal was female. The big surprise was that male mice actively approached the other animal, despite the perceived potential danger.

Image by Charles Williams via flickr (accessed under CC BY 2.0)

Looking at the blood of these mice, the scientist noticed an important difference: the immune cells of the male mice were more activated than those of their female counterparts. In particular, one of these immune cells, called neutrophils, showed signs of activation. Neutrophils can be thought of as one of the first lines of defence, the attack dogs of the immune system, with an arsenal of weapons at their disposal, most notably a stringy network of fibres with which they can trap their enemies in a process called NETosis. But more than that, they can talk to and activate other cells of the immune system via an array of molecular antennas on their surface. In their blood analysis, the scientists noticed that one of these molecules, NB1 or CD177, was significantly elevated in the male animals. They followed this up by repeating the experiment with male mice that lacked the gene for CD177 and therefore didn't have this molecule on the surface of their cells. And lo and behold, this was enough to turn their behaviour around 180°, and they showed the strong avoidance behaviour that had previously been seen in the female mice.


Based on previous knowledge and their own observations, they concluded that the CD177-carrying neutrophils must be talking to another type of immune cell, the T-cell. T-cells can do many things, one of which is to produce cytokines, secreted molecules that send signals to other cells. They found that crosstalk between neutrophils and T cells led to the release of a cytokine called interferon gamma (IFNG). Interestingly, INFG had previously been shown to also control the activity of neurons. Through many complicated experiments using a whole toolbox of biological sensors, Bin Wu's group realised that the released INFG blunts neuronal activity that would normally lead to avoidance of a threat, ultimately leading to the approaching behaviour seen in male mice.


However, understanding this mechanism didn't explain why this was only seen in males and not females. One major difference between the sexes is the level of sex-specific hormones, so they looked for the control of the androgen hormone, testosterone. What they found was clear: a stressed mouse (male or female) with elevated levels of the typical male hormone testosterone was more risk-taking than any of the control animals.


The effect can be summarised as follows: in male mice, a social threat induces increased levels of stress-related molecules and testosterone, both of which influence neutrophils to get ready to fight and also activate other parts of the immune system, one of which are T-cells that produce IFNG, which signals the brain to approach a threat. This makes a lot of sense, in a situation where you might be injured, it is beneficial to have the paramedics, the immune system, at the ready.

Humans show similar patterns

So what does this mean for you and me? Does this apply to human beings? Is the above-mentioned masculine honour ideology of fight or flight now a social concept or governed by biological processes? Well, Bin Wu's team also tried to peel away the top layer of these questions in their paper. Using blood samples from patients undergoing fear exposure therapy, they showed that male patients' neutrophils showed more variance in activation, response to stress and male sex hormones, suggesting similar mechanisms to those in the experimental mice. However, as the human psyche and behaviour is much more complex than that of mice, other factors may have a strong influence.


However, this superficial study could shed light on the unequal distribution of anxiety treatment rates between the sexes. Women are almost 70% more likely to be treated for anxiety disorders [3]. The differences found in this research paper could explain why men with anxiety have different coping strategies that lead to less active treatment, and so this study could pave the way for new treatment options.

What if it's missing?

Another aspect of my own research on neutrophils is the fact that, at least in Europe, 5-10% of the total population lacks the gene for CD177 [4]. Assuming that the results of this study are correct and that the mechanism is conserved in humans, one would expect to see a strong avoidance response to social threat in about 5% of the male population. Until a behavioural scientist goes out of his way to show this, I have to believe that the human mind, in all its complexity, is controlled by far more factors than a simple molecule produced by neutrophils.

1. Barnes, C. D., Brown, R. P., & Osterman, L. L. (2012). Don’t tread on me: Masculine honor ideology in the U.S. And militant responses to terrorism. Personality and Social Psychology Bulletin, 38(8), 1018–1029. https://doi.org/10.1177/0146167212443383
2. Wu, B., Meng, L., Zhao, Y., Li, J., Tian, Q., Pang, Y., Ren, C., Dong, Z., 2025. Meningeal neutrophil immune signaling influences behavioral adaptation following threat. Neuron 113, 260-276.e8. https://doi.org/10.1016/j.neuron.2024.10.018
3. Pesce, L., Veen, T. van, Carlier, I., Noorden, M.S. van, Wee, N.J.A. van der, Hemert, A.M. van, Giltay, E.J., 2016. Gender differences in outpatients with anxiety disorders: the Leiden Routine Outcome Monitoring Study. Epidemiology and Psychiatric Sciences 25, 278–287. https://doi.org/10.1017/S2045796015000414
4.Bai, M., Grieshaber-Bouyer, R., Wang, J., Schmider, A.B., Wilson, Z.S., Zeng, L., Halyabar, O., Godin, M.D., Nguyen, H.N., Levescot, A., Cunin, P., Lefort, C.T., Soberman, R.J., Nigrovic, P.A., 2017. CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation. Blood 130, 2092–2100. https://doi.org/10.1182/blood-2017-03-768507