Mice that survive infection transmit stronger immunity


MIce that recovers from infection can impart stronger immunity to their future puppies, according to a new study that expands the known effects of epigenetics in mammals.

“We wanted to test whether we could observe the inheritance of certain traits in subsequent generations, say independently of natural selection,” explains Jorge Dominguez-Andres, immunologist at the Radboud University Nijmegen Center in the Netherlands and co-author of the study. . “And what we observed was that the offspring of the mice that survived the infection were more resistant to the infections.”

The transgenerational transmission of immune-related traits has already been observed in plants, birds and invertebrates, including flies, beetles and worms. To test whether a similar mechanism works in mammals, Dominguez-Andres and his colleagues exposed adult mice to infectious fungi or zymosan, yeast particles used to stimulate the immune system. When either parent was subjected to the actual or simulated infection, the offspring showed a stronger immune response to potential pathogens, including E. coli bacteria than controls whose parents had not been challenged by the immune system. They had lower numbers of bacteria in their lungs and liver, as well as higher concentrations of immune cells and pro-inflammatory cytokines. The effect persisted further: the offspring of these second generation mice also showed a lower bacterial load after infection.

“I’m really curious to see how the scientific community sees this article. I’m sure there will be criticism, ”says Dominguez-Andres. The new article was only accepted for publication after the authors replicated the experiments, originally conducted at the University of Athens, in a separate laboratory from the University Hospital in Lausanne, Switzerland.

The study, published today in Natural immunology, might startle because it refers to Jean-Baptiste Lamarck, a French naturalist who proposed that organisms pass on characteristics acquired during their lifetime to their offspring. So, for example, a giraffe that constantly stretched the muscles in its neck to reach tall leaves would move onto a longer neck. Lamarckism is often presented as a competitor of Darwin’s theory of natural selection.

The authors write in the article: “Our data suggest the existence of Lamarckian mechanisms modulating immunological traits over generations that may result in evolutionary benefits. ”

“This should be the subject of a lot more research in different locations with different strains of mice grown under different conditions,” Dominguez-Andres said. “The results could probably differ depending on the settings. But we are confident and convinced it would recur with other types of mice and other species of pathogens.

In the meantime, “I think it sounds compelling,” says Oded Rechavi, a neurobiologist at Tel Aviv University who studies transgenerational inheritance and was not involved in the study. “You can see that they applied several different techniques and checked it in a lot of different directions. ”

Deepshika Ramanan, a microbiologist who studies the non-genetic transfer of immunological traits at Harvard Medical School and who was also not part of the study, agrees: “It’s not a far-fetched idea because it is. produced in insects and birds, etc.

A weakness of the study, she says, is that the results do not clearly show how the enhanced immunity is transferred from parent to offspring.

Tests in progeny mice showed that the stronger response to infection was associated with altered patterns of gene expression in myeloid cells in the bone marrow, which are known to be important for a phenomenon known as immunity trained, in which the innate immune system develops a “memory” of pathogens to stimulate future responses.

This does not explain how the mice passed on trained immunity to offspring that had never been directly infected. The study found that the fungal infection induced changes in sperm DNA methylation, an epigenetic process that can alter the way genes are expressed in offspring.

But Ramanan points out that the female mice that recovered from the infection in the study also produced offspring with a fortified immune system. “They say it’s through the semen, but I feel like there is still work to be done on how mothers pass it on,” she says.

Dominguez-Andres says his group is now working to try to better understand the epigenetic mechanism involved. They are also planning new experiments to check whether the age of mice when exposed is important and whether parental infections affect aging and inflammation in offspring mice. “And, of course, to what extent does that happen in humans.”

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