Home Lifestyle Health Study May Explain How Infections Reduce Autism Symptoms

Study May Explain How Infections Reduce Autism Symptoms

For many years, some parents have noticed that their autistic children’s behavioral symptoms diminished when they had a fever. This phenomenon has been documented in at least two large-scale studies over the past 15 years, but it was unclear why a fever would have such an effect.

A new study from MIT and Harvard Medical School sheds light on the cellular mechanisms that may underlie this phenomenon. In a study of mice, the researchers found that in some cases of infection, an immune molecule called IL-17a is released and suppresses a small region of the brain’s cortex that has previously been linked to social behavioral deficits in mice.

Gloria Choi, the Samuel A. Goldblith Career Development Assistant Professor of Applied Biology and an assistant professor of brain and cognitive sciences at MIT, said:

Although findings in mice do not always translate into human treatments, the study may help to guide the development of strategies that could help to reduce some behavioral symptoms of autism or other neurological disorders, says Choi, who is also a member of MIT’s Picower Institute for Learning and Memory.

In a study of mice, the researchers found that in some cases of infection, an immune molecule called IL-17a is released and suppresses a small region of the brain’s cortex that has previously been linked to social behavioral deficits in mice. (Image: via pixabay / CC0 1.0)
In a study of mice, the researchers found that in some cases of infection, an immune molecule called IL-17a is released and suppresses a small region of the brain’s cortex that has previously been linked to social behavioral deficits in mice. (Image: via pixabay / CC0 1.0)

Choi and Jun Huh, an assistant professor of immunology at Harvard Medical School, are the senior authors of the study, which appears in Nature. The lead authors of the paper are MIT graduate student Michael Douglas Reed and MIT postdoc Yeong Shin Yim.

Immune Influence

Choi and Huh have previously explored other links between inflammation and autism. In 2016, they showed that mice born to mothers that experience a severe infection during pregnancy are much more likely to show behavioral symptoms such as deficits in sociability, repetitive behaviors, and abnormal communication.

They found that this is caused by exposure to maternal IL-17a, which produces defects in a specific brain region of the developing embryos. This brain region, S1DZ, is part of the somatosensory cortex and is believed to be responsible for sensing where the body is in space. Choi said:

A link between infection during pregnancy and autism in children has also been seen in humans. A 2010 study that included all children born in Denmark between 1980 and 2005 found that severe viral infections during the first trimester of pregnancy translated to a threefold increase in risk for autism, and serious bacterial infections during the second trimester were linked with a 1.42-fold increase in risk.

These infections included influenza, viral gastroenteritis, and severe urinary tract infections. In the new study, Choi and Huh turned their attention to the often-reported link between fever and the reduction of autism symptoms. Choi said:

The researchers began by studying mice that exhibited behavioral symptoms due to exposure to inflammation during gestation. They injected these mice with a bacterial component called LPS, which induces a fever response, and found that the animals’ social interactions were temporarily restored to normal.

Further experiments revealed that during inflammation, these mice produce IL-17a, which binds to receptors in S1DZ — the same brain region originally affected by maternal inflammation. IL-17a reduces neural activity in S1DZ, which makes the mice temporarily more interested in interacting with other mice.

A link between infection during pregnancy and autism in children has also been seen in humans. (Image: via pixabay / CC0 1.0)
A link between infection during pregnancy and autism in children has also been seen in humans. (Image: via pixabay / CC0 1.0)

If the researchers inhibited IL-17a or knocked out the receptors for IL-17a, this symptom reversal did not occur. They also showed that simply raising the mice’s body temperature did not have any effect on behavior, offering further evidence that IL-17a is necessary for the reversal of symptoms. Choi said:

Dan Littman, a professor of immunology at New York University, who was not involved in the study, said:

Behavioral Effects

The researchers then performed the same experiments in three additional mouse models of neurological disorders. These mice lack a gene linked to autism and similar disorders — either Shank3, Cntnap2, or Fmr1. These mice all show deficits in social behavior similar to those of mice exposed to inflammation in the womb, even though the origin of their symptoms is different.

Injecting those mice with LPS did produce inflammation, but it did not have any effect on their behavior. The reason for that, the researchers found, is that in these mice, inflammation did not stimulate IL-17a production. However, if the researchers injected IL-17a into these mice, their behavioral symptoms did improve.

A link between infection during pregnancy and autism in children has also been seen in humans. (Image: via pixabay / CC0 1.0)
A link between infection during pregnancy and autism in children has also been seen in humans. (Image: via pixabay / CC0 1.0)

This suggests that mice who are exposed to inflammation during gestation end up with their immune systems somehow primed to more readily produce IL-17a during subsequent infections. Choi and Huh have previously shown that the presence of certain bacteria in the gut can also prime IL-17a responses.

They are now investigating whether the same gut-residing bacteria contribute to the LPS-induced reversal of social behavior symptoms that they found in the new Nature study. Huh said:

Choi’s lab is also exploring whether any immune molecules other than IL-17a may affect the brain and behavior. Choi said:

Provided by: Anne Trafton, Massachusetts Institute of Technology [Note: Materials may be edited for content and length.]

Follow us on Twitter or subscribe to our weekly email  

Troy Oakes
Troy was born and raised in Australia and has always wanted to know why and how things work, which led him to his love for science. He is a professional photographer and enjoys taking pictures of Australia's beautiful landscapes. He is also a professional storm chaser where he currently lives in Hervey Bay, Australia.

Most Popular

WHO Continues to Defer to Beijing in COVID-19 Origin Investigation

Close to a year after the COVID-19 outbreak in Wuhan, China, the World Health Organization has been unable, or unwilling, to either...

Economic Talks in Washington Strengthen US-Taiwan Relations

On Friday, Nov. 20, Taiwan officials participated in the island state’s first Economic Prosperity Partnership (EPP) Dialogue with the United States in...

Biden Plans Congressional Bailout to Forgive Student Loans

U.S. Democratic presidential contender Joe Biden has said that as president, he would forgive $10,000 in individuals’ student loans, including more relief...

No Drinking! No Fighting! The Laws of Early Edo Japan to Keep the Peace

An early Edo period document stipulating the Hosokawa clan code of conduct for vassals dispatched on a national project to rebuild Sunpu...