Epigenetic inheritance also shapes the immune system: this “rapid form” of genetic adaptation allows acquired resistance to be passed on to offspring after infection, according to a study on mice. After they had overcome a fungal infection, males inherited an improved immune response to the next generations through epigenetic modifications of their sperm DNA. The researchers say the results can probably also be transferred to humans.
For a long time, the sequence of the DNA bases in the genome was considered to be the only basis for the computer science of life. But it is now clear: There is also a “second level” of genetics – epigenetics. Many studies have shown that certain control mechanisms of the genetic code shape the characteristics of living things. These so-called epigenetic factors are based, among other things, on chemical switch molecules that sit on the DNA and control the activity of certain hereditary factors. In the course of life, these genetic rule elements can settle on the genetic make-up through certain factors such as diet, stress or diseases and thus have a lasting effect on the characteristics of a living being.
Many elements of the epigenetic switch system are canceled again when the generation changes – but some imprints are transferred to the offspring in different organisms. Even in mammals, including humans, there are indications that epigenetic changes in subsequent generations influence the metabolism, for example. A transfer of infection resistance to the next generation, however, has so far only been demonstrated in plants and invertebrates. An international team of researchers led by Mihai Netea from the Radboud Center for Infectious Diseases in Nijmegen has now closed this gap in mammals.
Immunization is passed on to offspring
For their study, the scientists infected male mice with the widespread fungal pathogen Candida albicans (thrush fungus), which can also cause symptoms in humans. After surviving the infection, the animals were then mated with healthy females. The researchers were then able to compare the offspring resulting from these compounds with offspring from pairs of mice that had not previously been infected with Candida. In order to investigate the reactions of the immune system experimentally, she infected males of the next generation of mice with E. coli bacteria.
It initially showed: “The descendants of the male mice that were previously exposed to Candida were significantly better protected from E. coli infection than the offspring of the uninfected male mice,” reports Netea. Further investigations showed that the protective effect was retained in the next generation. The team then investigated the principles on which the transmission of immunization to future generations could be based. To do this, they first examined the immune cells of the test animals using molecular biological and genetic methods.
The offspring of the previously infected mice showed a noticeable activation of a protein complex in immune cells, which plays an important role in the defense against pathogens. In addition, it became apparent that in these animals the activity of genes that have a function in the fight against infection was also upregulated. Especially with the precursors of a certain type of immune cell – the monocytes – it became apparent that inflammation-associated genes are read better than with the offspring of the uninfected fathers. “This shows that the monocyte precursors of the immune system are epigenetically reprogrammed if the fathers were previously infected with Candida albicans”, sums up co-author Andreas Schlitzer from the University of Bonn.
Programming the sperm DNA
But how is the epigenetic imprint passed on? When it came to this question, the focus was on the male mice’s sperm: The researchers examined the activity of genes in the sperm cells of the animals previously infected with Candida. Specifically, they used molecular genetic methods to investigate the extent to which epigenetic switch elements (methyl groups) blocked access to certain genetic makeup. “We noticed a shift in the gene markings,” reports co-author Jörn Walter from Saarland University in Saarbrücken. Specifically: offspring of Candida-infected male mice showed fewer blockages in gene regions that are known for their function in inflammatory processes and the maturation of monocytes.
“The study shows for the first time in mammals that adaptations to infectious diseases are passed on to offspring,” says Netea, emphasizing the importance of the results. She and her colleagues want to stay true to the research topic, because there are still a few questions to be answered. Among other things, they want to investigate how the epigenetic information gets into the bone marrow – the birthplace of many immune cells. In addition, the scientists have not yet been able to say to what extent the knowledge gained in mice can be transferred to humans. But they are at least fundamentally confident: “We assume that they are transferable. Because the mechanisms and cells of the immune system involved are very similar in mice and humans, ”says Schlitzer.
Source: Rheinische Friedrich-Wilhelms-Universität Bonn, specialist article: Nature Immunology, doi: 10.1038 / s41590-021-01052-7