Brain-immune cross-talk may build resilience against stress.


We tend to assume our thoughts and feelings are controlled almost exclusively by our brains. But peripheral systems, such as our hormonal and immune systems also influence how we think, feel and behave.

Communication between the brain and rest of the body goes both ways. Psychological stress and stress hormones alter the status of the immune system. In turn, an agitated immune system will impact brain function and structure.

Bidirectional neuro-immune pathways serve to achieve internal homeostasis or biological ‘equilibrium’. Disequilibrium, if sustained or severe, results in disease.

A team of researchers from NIH–DHHS facility in Bethesda Maryland recently explored the idea of bidirectional brain-immune communication to see if cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and brain function.

To generate ‘stressed mice’, pairs of mice were housed together: a dominant aggressive mouse with an ‘intruder’ who became stressed and ‘socially defeated’. Lymphocytes (a type of immune cell) were isolated from the stressed mouse and injected into another healthy ‘non-stressed out’ host mouse.

Unexpectedly, the stressed immune cells didn’t confer anxiety and depression, instead they appeared to protect against stress. They built resilience in the host mouse.

The recipient mice showed:

  • less anxiety and depression-related behaviours and increased sociability 
  • reduced pro-inflammatory cytokine levels in the blood
  • increased cell proliferation in the hippocampus (of the like seen with anti-depressant use)
  • microglia (a immune cell found exclusively in the brain) skewed toward an anti-inflammatory, neuro-protective phenotype

Remarkably, the behaviours and biochemical profiles associated with stress were reversed in the mice receiving cells from stressed donors. As the authors say “In effect, equilibrium was restored.

These results suggests that psychological stress can modify adaptive immune cells in a long-lasting manner that may boost resilience to stress.  

“…psychological stress might induce an immunological memory within the adaptive immune system that supports stress resilience.”

The team wonders if differences in the adaptive immune system may account for different susceptibilities to stress and resilience, and could potentially be useful in identifying at-risk individuals. Finally, they suggest the immune system could be a viable target for antidepressant therapies.

Brachman et al. Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice. The Journal of Neuroscience, January 28, 2015 • 35(4):1530 –1538
Image credit: Nick Russill

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  1. rick m. on April 24, 2015 at 4:43 am

    How do I “like” this article? I found it very interesting.

    • Sarah McKay on April 24, 2015 at 12:19 pm

      I’d say this comment will do!!

    • Amanda on April 29, 2015 at 12:53 pm

      Great article. As a coach, helping my clients positively manage stress, while understanding brain behaviours with adaptive thinking, is paramount to their success. Resilience is an interesting issue and as I also do a lot of work in Grief Recovery. A lot of research also indicates that resilience is an important factor in integrating loss; that those with exposure to grief and its psychological impact early on in life, tend to cope better than those that experience a ‘blessed’ life.

      • Sarah McKay on May 1, 2015 at 10:16 am

        Yes…the research surrounding resilience is fascinating. Thankfully they talk about it at my little boy’s school – such a key life skill to learn.

      • Lorry on September 3, 2015 at 8:33 am

        I have only just happened upon this article, and felt I should offer my experience with grief as a 5 year old child. My elder brother died when I was 5, after he endured a short life of 9 years of ill-health. I remember accepting his death without too much emotional reaction, being surrounded and distracted by 5 other siblings, 2 of them older then me. However, I distinctly remember that in the following months, I suddenly understood the fact that we would all die one day, and I then developed a paralysing fear of my parents dying. This fear crippled me for many years, preventing me from enjoying many childhood opportunities, interrupting my sleep, and withdrawing from activities with friends that involved staying away from home. While out walking with my family, I always walked last in the line, so that I could see that everyone was in view. If the house was quiet when I woke in the mornings, I would often wonder if I was the only person alive. Clearly, I was a very emotionally-troubled child, and many nights when I sought comfort from my parents, they would talk about life and death with me, and try to help me understand life. But the fear remained underneath, and still today, though I have survived the loss of both parents, I remain a fearful person.
        i am interested in the link between gut and brain health, and emotional resilience, and think that I had poor gut health generally all my life, which possibly contributed to me living as though on an emotional roller-coaster. Fear would always begin in my stomach as a child, and would reduce my appetite greatly.
        To get to the crux of my query though….it seems that my early life experience of psychological stress did not help my immune system to adapt to withstand later-life stress, nor did it build resilience in me. Might it be that for equilibrium to be restored, we also need to improve the gut health to support the physical body’s ability to build resistance emotionally?
        As Joan Taylor mentioned in her response, below, perhaps other factors might impact individuals differently, depending on the demands they face in their daily life. It is an interesting field of study, but I think more consideration needs to be given to other factors influencing human life, which laboratory mice will not experience.
        Thanks for all the information you source and post on your site, it’s very interesting!!!

  2. Rosanna on April 29, 2015 at 3:13 pm

    I’m so happy I found your website. I’m a transformational therapis and I’ve been using neuroscience to help my clients heal. This is a wonderful site and I am learning much from it.

    Will certainly share this new discovery in my website and social media!

    • Sarah McKay on May 1, 2015 at 10:17 am

      I’m delighted you found me too Rosanna – feel free to share far and wide 🙂

  3. joan taylor on May 10, 2015 at 9:12 pm

    Hi Sarah, First off wonderful job, good work!
    On this matter of the stressed mice, I have found that; when under life threatening stress, the (my) immune system has taken over and during the time of extreme stress, I never experience any diseases such as the common cold, flu, etc. during the first year, (my thinking at the time was that my immune system was very strong) I was so pleased. Than during the second year, the stress became a slight bit less…Bam, I suddenly got the flu, and it went into pneumonia ( my organs of grief). The other, very bothersome issue has become my intestines start holding on to food, bowels shut down and sudden weight gain in jumps of 5lbs at a time, even with exercise. Now I spent last year again, in a very stressful, life threatening arena, and the depression showed up in full force, my mind did not support any positive thoughts, I started giving up being strong, courageous, and positive. I seemed not to have any control over the doom and gloom, although I tried to act positive, telling myself I know better, and I am strong, and worthy. I got one small cold, but the strength to push forward is weak, my drive is gone and the weight has soared dangerously, and my physical health is an issue.

    My question is : For how long did the “stressed Mouse” study carry on for, and if it is ongoing I wonder what it showed as the mouse carried this burden, and aged. Also, when we approach the “golden” years and all systems are wearing out, how does stress effect us, and is it in a different way. I think this needs to be studied for age does change all systems, and depression is prevalent, and is it only in those who struggle for survival ( economically & socially) while those with less issues, who can take trips, and enjoy life without worries of losing their homes, and with the diminishing of close friends etc., if so how can we override the decent?

    Again thank you for your energy, and focus on this important topic of study.

    Joan Taylor

  4. Astrid Larsen on May 14, 2015 at 6:46 pm

    Hi Sarah,

    I have recently subscribed to your blog, am visiting here for the first time, and am so excited to take this journey into lay man’s neuroscience and to make space in my life consciously to nurture my brain’s health – and love it!

    Fascinating article on resilience! I’m interested to read your reply to Joan’s question too.

    Thank you for your offerings!


    • Sarah McKay on May 15, 2015 at 9:28 am

      You’re welcome Astrid – glad to have you on board too!

  5. Elisabeth on May 4, 2016 at 7:37 pm

    Excuse but I got a bit stupid question, you didn’t practice meditation for some specific reasons such as side effect, or you just only wanted to try those other methods you listed there, thanks!

    • Sarah McKay on May 4, 2016 at 9:32 pm

      Mostly because I don’t enjoy it much – I’d rather do the other things I’ve listed here 🙂

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