Summer School in Sardinia: A four star hotel with pool, all-inclusive food and wine, a private beach in the most fancy part of the whole island – sounds like some pretty good “holidays”. This assumption was not even close since it turned out to be one of the most intense weeks of my life. Don’t get me wrong – it was an amazing experience! I enjoyed every talk given by the board, which consisted of many outstanding scientists, and also sharing my experience with other PhD students from all over Europe. I even enjoyed the late poster sessions with a glass of wine! However, it was a very demanding week, both physically and mentally, and indeed, I needed almost two weeks to recover.
During the week I learned a lot more about immunology. But apart from the impact on my knowledge of the immune system, it made me wonder which impact this intense week of summer school might have had on my immune system. Here are just some of the factors which have already been described to have an influence:
Saturday, 3:30 am: my alarm clock rang. At this very moment I was not sure if the summer school was worth taking a flight at 6 am in the morning. I got up, had a shower and already on the way to the airport I had the feeling that I started into this week with a lack of sleep. I had anticipated that I would not have the opportunity to catch up on my sleep as the school progressed – and I was right!
Scientific studies in mouse and human on the impact of sleep deprivation are inconsistent, mainly because they differ largely in the methods used to disturb sleep. Furthermore, measurements are mostly done at a few time points, so that transient changes may not be detected. However, most studies are pointing towards an increase in leukocyte numbers in the blood after several nights of restricted sleep. Whereas B and T cell populations are mostly reported not to be altered by sleep, numbers of circulating monocytes and neutrophils are increased after prolonged wakefulness. In line, levels of pro-inflammatory cytokines, for example TNF and IL-6, were shown to be elevated. A recent publication in Nature investigated a potential molecular mechanism on how sleep fragmentation influences hematopoiesis. They discovered that sleep fragmentation inhibits the production of the hypothalamic neuropeptide hypocretin. Without its inhibitory effect on pre-neutrophils, there is an increase in neutrophil and monocyte maturation in the bone marrow. Consequently, sleep deprived mice exhibit higher numbers of these cell types in the circulation and also develop larger atherosclerotic lesions.
Taking all this together I think that my sleeping behavior negatively influenced my immune system. What I can definitely say is that I needed a whole day in bed after coming back home 🙂
Although the nights were quite short I never skipped breakfast – it was just too good. Also, the lunch and dinner buffets were sumptuous! But as a lover of the Italian cuisine, I didn’t expect anything else. All these fruits and vegetables, the home-made pasta and fresh fish made it impossible not to enjoy every meal. And of course there was wine flowing every evening. The Mediterranean diet is famous for its benefits including heart and brain health and prevention of cancer and chronic diseases. Here, I will discuss two specific components of the diet and how they impact the immune system.
Plant and fish oils
N-3 polyunsaturated fatty acids (n-3 PUFAs) cannot be produced by the mammalian system, hence we rely on taking them up with food. The essential α-linolenic acid (ALA) is produced by plants and is therefore enriched in nuts and plant-based oils whereas fish oils contain both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Enrichment of EPA and DHA in the plasma membrane of immune cells is associated with a decrease in the metabolism of the pro-inflammatory arachidonic acid and reduction of COX2 expression, leading to inhibition of the production of arachidonic acid-derived eicosanoids such as PGE2. Furthermore, many studies show an inhibitory effect of EPA and DHA on the production of TNF, IL-6 and IL-1β via regulation of NF-κB. There is evidence that DHA inhibits the dimerization and the recruitment of TLR4 into lipid rafts, which is essential for signal transduction. Moreover, DHA might restrain NF-κB activation via PPAR-γ. A study published in Immunity in 2013 could show that ω-3 FAs can suppress priming and activation of the NLRP3 inflammasome. Moreover they demonstrated beneficial effects of ω-3 FA on metabolic stress-induced inflammation and insulin resistance in a mouse model using high-fat diet.
Wine contains various ingredients which can affect the immune system. There are many studies analyzing the effect of alcohol on immune cells. The consensus is that chronic (more or less excessive or abusive) alcohol consumption has detrimental effects including decrease and impairment of almost all immune cells that can lead to increased susceptibility to infections. In contrast it also stimulates the production of pro-inflammatory cytokines, which leads to tissue damage. However, there is also evidence that moderate consumption of red wine has anti-inflammatory effects. This may not be due to its alcohol content but rather to the abundance of polyphenols and anti-oxidants. One of these compounds is Resveratrol. Several studies show that Resveratrol can attenuate inflammation by interacting with Sirtuin-1, which can then modulate different pathways including the NF-κB and AMPK signaling. A recent publication even describes a beneficial effect of Resveratrol treatment on the gut microbiota. In this study, they showed that Resveratrol could reverse microbial dysbiosis in a model of colitis. This was accompanied by an increase in regulatory T cells and a decrease in Th17 cells leading to mitigated symptoms in treated mice.
Obviously, there are many more nutritional factors that might have had effects on my immune system. The general effect on my body was, however, that I gained maybe one or two kilograms because I could not resist the pasta. Also, I am not quite sure if the amount of wine I drank would still be considered as moderate but it definitely stimulated all of us to discuss our posters and to ask questions we might not have asked if we would have been completely sober!
I was really excited to go to Sardinia because of the weather. In the middle of May I expected the weather to be sunny and some degrees warmer than in Germany. Maybe even warm enough to take a swim in the sea or to spend the afternoon break in the pool. However, I was deeply disappointed when I checked the forecast – 15°C, clouds and rain. Luckily, we did have some hours of sun, so packing my swimsuit was not a complete waste of space in my suitcase. And I had the feeling that I got a little tan as well.
We have all experienced the unpleasantness of sunburn and it’s not surprising that this has some negative effects on our body. High UV radiation leads to local inflammation and systemic immunosuppression. However, there are studies that also describe a beneficial effect of repetitive low dose UV exposure. It was shown that low dose UV radiation could strengthen the barrier function of the skin by inducing vascularization and the production of antimicrobial peptides. Furthermore, UV light promotes the synthesis of vitamin D. Many immune cells express vitamin D receptors, which can be upregulated after immune cell activation. Vitamin D exposure is associated with a tolerogenic immune response characterized by inhibition of Th1 and Th17 cells and induction of Treg cells.
Considering the very few hours of sun I managed to soak up, I would consider my UV exposure as low dose, so maybe beneficial for my immune system. Still, the sun definitely had a beneficial effect on my summer mood!
During the week in Sardinia there where millions of little factors that influenced my immune system, some beneficial and some detrimental. In the end I couldn’t really feel a difference – but at least I did not get sick afterwards.
In general, the summer school had a very positive effect on my motivation to do research, to network and to continue learning new and interesting things about our immune system!
Author: Nina Offermann
- Alrafas, H.R., Busbee, P.B., Nagarkatti, M., and Nagarkatti, P.S. (2019). Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells. J. Leukoc. Biol. JLB.3A1218-476RR.
- Artero, A., Artero, A., Tarín, J.J., and Cano, A. (2015). The impact of moderate wine consumption on health. Maturitas 80, 3–13.
- Barr, T., Helms, C., Grant, K., and Messaoudi, I. (2016). Opposing effects of alcohol on the immune system. Prog. Neuro-Psychopharmacology Biol. Psychiatry 65, 24Barr, T., Helms, C., Grant, K., and Messaoudi, I.
- Malaguarnera (2019). Influence of Resveratrol on the Immune Response. Nutrients 11, 946.
- Romeo, J., Würnberg, J., Nova, E., Díaz, L.E., Gómez-Martinez, S., and Marcos, A. (2007). Moderate alcohol consumption and the immune system: A review. Br. J. Nutr. 98.
- Szabo, G., and Saha, B. (2015). Alcohol’s Effect on Host Defense. Alcohol Res. 37, 159–170.
- Besedovsky, L., Lange, T., and Born, J. (2012). Sleep and immune function. Pflugers Arch. Eur. J. Physiol. 463, 121–137.
- Besedovsky, L., Lange, T., and Haack, M. (2019). The Sleep-Immune Crosstalk in Health and Disease. Physiol. Rev. 99, 1325–1380.
Plant and fish oils:
- Calder, P.C. (2004). Omega-3 Polyunsaturated Fatty Acids, Inflammation and Immunity. Fat. Acids Lipids – New Find. 109–116.
- Calder, P.C. (2017). Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem. Soc. Trans. 45, 1105–1115.
- Yan, Y., Jiang, W., Spinetti, T., Tardivel, A., Castillo, R., Bourquin, C., Guarda, G., Tian, Z., Tschopp, J., and Zhou, R. (2013). Omega-3 Fatty Acids Prevent Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome Activation. Immunity 38, 1154–1163.
- Cela, E.M., Gonzalez, C.D., Friedrich, A., Ledo, C., Paz, M.L., Leoni, J., Gómez, M.I., and González Maglio, D.H. (2018). Daily very low UV dose exposure enhances adaptive immunity, compared with a single high-dose exposure. Consequences for the control of a skin infection. Immunology 154, 510–521.
- Prietl, B., Treiber, G., Pieber, T., and Amrein, K. (2013). Vitamin D and Immune Function. Nutrients 5, 2502–2521.