Analysis

Severe Infection in Pregnancy Could Contribute to Autism

Research by Pew scholar shows that prenatal inflammation in mice could be a factor in development of the disorder

An abstract depiction of chemicals secreted by maternal immune cells and fetal brain development.

Jun Huh and Gloria Choi

For 11 years, nations and organizations have observed World Autism Awareness Day on April 2 to increase understanding of the disorder and acceptance of people with autism. The United Nations marked the day for the first time in 2008 to celebrate diversity and to promote the rights and well-being of those with learning differences and developmental disabilities.

One of the biggest mysteries surrounding autism continues to be its cause. Research indicates that there is not just a single cause, but rather a combination of genetic and environmental factors that can contribute to the onset and progression of autism spectrum disorders.

Jun Huh, a 2016 Pew scholar, has focused his work on how the maternal immune system can influence the developing brain. In two studies published last year, Huh and his colleague Gloria Choi help to explain the link between severe infection during pregnancy and autism, and shed new insight into ways to prevent the disorder.

Throughout a woman’s pregnancy, molecules pass through the placenta. Although most are meant to nourish the fetus, some harmful substances also can cross this barrier. Research has shown that pregnant mice infected with viruses can give birth to pups that exhibit anxiety, repetitive behaviors, and avoidance of social engagement—actions that resemble the symptoms of autism spectrum disorders in humans.

In earlier work, Huh, who recently moved his laboratory from the University of Massachusetts Medical School to the Evergrande Center for Immunologic Diseases at Harvard Medical School, determined that a type of immune cell called Th17 drives the inflammatory response within the pregnant woman’s body during an infection. Th17 secretes a molecule called IL-17, which can interact with cells in the developing fetal brain to cause behavioral abnormalities.

In research published last year in Nature, Huh and colleagues set out to learn more about the affected region of the fetal brain called the cortical patches. By eliminating Th17 cells from the mother or blocking the activity of IL-17, the scientists saw a reversal of autistic-like symptoms in the mice offspring.

Huh also points to other factors that appear to contribute to the development of autism, which his group described in a second Nature paper. The authors note that not all offspring born from mice that had severe infections suffered from behavioral abnormalities and that other factors must be in play. They found that only the offspring from mothers harboring a specific type of bacteria in their gut showed abnormal behaviors; these bacteria are also known to stimulate Th17 cells’ production of IL-17.

Moving forward, Huh says he hopes to determine how IL-17 crosses the placenta from mother to fetus and how the molecule alters the development of the fetal brain. Such findings could lead to innovative approaches to preventing neurodevelopmental disorders, such as autism and schizophrenia, which an increasing body of work shows may be brought about by infection or inflammation in utero.

Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs.

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