Does an infection affect the immunization of subsequent generations? Researchers at Radboud University (Netherlands) have studied this together with the Universities of Bonn, Saarland (Germany), Lausanne (Switzerland), and Athens (Greece). Mouse fathers who had previously overcome an infection with fungi or were stimulated with fungal compounds passed on their improved protection to offspring across several generations. The team showed at the same time an improved immune response being passed on to the descendants. The study has now been published in the renowned journal Nature Immunology. Not just what is written in the DNA sequence is inherited. Scientific studies show that environmental influences are also passed on to the next generation. One example: children who grew in the womb during the hunger winter of 1944/45 show typical changes in their metabolism as an adaptation to food scarcity during development, and this is associated with a higher risk of diabetes and obesity. Epigenetic research investigates such relationships on the molecular level. It examines changes in gene function. “Not all areas of DNA are equally accessible for reading the genetic information,” explains Prof. Dr. Andreas Schlitzer of the LIMES Institute at the University of Bonn. The researchers infected male mice with thrush fungi (Candida albicans). After recovering from the infection, the animals were mated with healthy females. The researchers compared the resulting offspring with offspring from pairs of mice that were not infected previously with Candida. In order to investigate the status of the immune system experimentally, the team infected the males of the subsequent generation of mice with coliform bacteria. “The offspring of the male mice previously exposed to Candida were significantly better protected from a subsequent E. coli infection than the progeny of the uninfected male mice,” says Prof. Mihai G. Netea of the Radboud Center for Infectious Diseases. This effect was still evident in the next generation. How does this transmission of immunization to subsequent generations work? The team examined typical immune cells such as monocytes or neutrophils. No differences were detectable between the offspring of Candida-infected male mice and the non-infected control group. However, in the offspring of the previously infected mouse fathers, the MHC class II complex was upregulated, which activates parts of the immune system. In addition, the activity of genes involved in inflammation was found to be upregulated in the offspring of Candida-infected male mice. In the offspring of fathers previously infected with thrush fungi, it was found that genes associated with inflammation were easier to read in monocyte progenitors than in sons of uninfected fathers. “This shows that monocyte precursors are epigenetically rewired if the fathers have previously undergone infection with Candida albicans,” Schlitzer says. The researchers do not know if the findings obtained in mice can be transferred to humans. “But we are assuming that this is the case,” Schlitzer says. “The immune system mechanisms and cells involved are very similar in mice and humans.”
https://www.radboudumc.nl/en/news-items/2021/epigenetics-immunization-is-passed-on-to-offspring
