Muscles support a strong immune system
In the fight against cancer or chronic infections, the immune system must be active over long periods of time. However, in the long run, the immune defence system often becomes exhausted. Scientists at the German Cancer Research Center (DKFZ) have now found initial evidence in mice that skeletal muscles help to keep the immune system functional in chronic diseases.
Sceletal muscle seen through a light microscope
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In many cases, severe weight loss and a decrease in muscle mass are the result of cancer or dangerous infections. In addition to this process known as cachexia, patients often suffer from a weakened immune system. One of the reasons for this is a loss of function of a group of T-cells, whose task it is to recognize and kill virus-infected cells or cancer cells.
The processes leading to loss of T-cell activity are still largely unexplained. However, first indications suggest that there is a connection with cachexia. "It is known that T-cells are involved in the loss of skeletal muscle mass. But whether and how, in turn, skeletal muscles influence the function of the T-cells is still unclear," explains Guoliang Cui from the DKFZ.
To find out, the scientists infected mice with lymphocytic choriomeningitis virus (LCMV). This method is a widely used model system to study the course of acute or chronic infections in mice. The researchers then analysed the gene expression in the skeletal muscles of the animals and found that in chronic infections, the muscle cells release an increased amount of the messenger substance interleukin-15. This cytokine causes T-cell precursors to settle in the skeletal muscles. As a result, they are spatially delimited and protected from contact with the chronic inflammation.
"If the T-cells, which actively fight the infection, lose their full functionality through continuous stimulation, the precursor cells can migrate from the muscles and develop into functional T-cells," said Jingxia Wu, lead author of the study. "This enables the immune system to fight the virus continuously over a long period."
So could regular training strengthen the immune system? "In our study, mice with more muscle mass were better able to cope with chronic viral infection than those whose muscles were weaker. But whether the results can be transferred to humans, future experiments will have to show," explains Guoliang Cui.
Wu J, Weisshaar N, Hotz-Wagenblatt A, Madi A, Ma S, Mieg A, Hering M, Mohr K, Schlimbach T, Borgers H and Cui G: Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion. Science Advances 2020; DOI: 10.1126/sciadv.aba3458
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
