Doubts are raised whether mice can actually inherit immunity

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RThe researchers failed to replicate the results of a landmark study that purported to show that mice that recover from an infection can pass on stronger immunity to their future puppies. According to a report published last week (January 20) in Natural immunology.

See “Mice that survive infection transmit stronger immunity”

“Even though we tried to look for evidence of transmission, I mean, there was literally nothing. It was like the most insignificant set of results we’ve ever had,” says Luis Barreiro, a geneticist at the University of Chicago who worked on the replication attempt. “That was a wacky idea to start with, I thought.”

The original study was published in Natural immunology in October. He reported the results of experiments that exposed adult mice to infectious fungi or zymosan, particles made from yeast used to boost the immune system. When either parent was subjected to real or simulated infection, the offspring showed a stronger immune response to potential pathogens, including E.coli bacteria, than controls whose parents had not been subjected to an immune system challenge. 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.

Transgenerational transmission of immune system-related traits had previously been observed in plants, birds, and invertebrates, including flies, beetles, and worms, but the October paper was the first to claim such an effect. in mammals, and it raised the question of whether the same mechanism might be at work in people. In fact, the results were so striking that the journal only accepted the article after key experiments, originally carried out at the University of Athens, were replicated in a separate laboratory at the University Hospital of Lausanne. , in Swiss.

Even though we tried to look for evidence of transmission, I mean, there was literally nothing. It was like the most insignificant set of results we’ve ever had.

—Luis Barreiro, University of Chicago

“The frustrating part of it all is that honestly I don’t really have a good explanation as to why the results are so different,” Barreiro says. “We did pretty much everything they did.”

The study’s original authors, led by immunologist Mihai Netea of ​​Radboud University, have published an accompanying response to the new report by Barreiro and colleagues. The response proposes that the different outcomes boil down to “elusive” effects of the environment such as differences in mouse substrains, housing, diets, or microbiomes. A careful reading of the methods in the two papers, for example, reveals that Netea and his colleagues used male mice that were six weeks old in their initial generation, while Barreiro’s first generation of mice were up to two weeks older and included both genders.

Netea says differences between the experimental protocols “certainly exist,” adding that he welcomes the new paper, as it’s important that details of both studies are released so other groups can dig deeper into precisely what’s behind it. contrasting results. “And then in the future, hopefully, we’ll understand where . . . the difference [is] coming,” he said.

Other researchers in the field agree that environmental factors could be responsible for the different results. “The lack of replication is important, but there are several reasons for this,” says Deepshika Ramanan, a microbiologist who studies non-genetic transfer of immunological traits at Harvard Medical School and was not involved in either study. “Changes in the environment of mice, particularly the microbiome, affecting reproducibility are quite common,” she notes.

Netea and Barreiro point out that the relationship between their groups is friendly and that they have cooperated with each other, including sharing data and experimental material.

“The only way to solve this problem is to do more studies, by different groups, while trying to carefully monitor environmental changes and effects,” says Ramanan.

The answer will not come soon. “The problem with these types of studies is that they are long,” says Netea. Both studies took around six years to complete, as the experiments required multiple generations of animals and each lasted over a year. “It will take time, but I think it’s worth it,” says Netea.

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