Trained Immunity Can be Passed to Offspring

Researchers at Radboud University in the Netherlands have shown that improved immune responses are passed to offspring. The study was published in Nature Immunology. 

The researchers infected male mice with thrush fungi Candida albicans. After recovering from the infection, the animals were mated with completely 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," reports researcher Mihai G. Netea. This effect was still evident in the next generation.

The team examined typical immune cells such as monocytes or neutrophils. While no differences were detectable between the offspring of Candida-infected male mice and the non-infected control, 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 also 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 summarizes.

In cooperation with Saarland University, the researchers investigated the gene activity of the sperm of mouse fathers infected with Candida. They analyzed the extent to which methyl groups blocked access to genes. "A shift in gene markers was evident here," says collaborator Jörn Walter. Offspring of Candida-infected male mice showed fewer gene blockages in gene regions important for inflammatory processes and monocyte maturation. 

"The study is the first to show in mammals that adaptations to infectious diseases are also passed on to the offspring," Netea says. In contrast to the classical theory of evolution, which assumes slow adaptation through changes in the genetic code, this involves very rapid changes via the epigenetic regulation of gene activities, irrespective of the genetic code. The researchers do not yet know whether the findings obtained in mice can also be transferred to humans.