The COVID-19 pandemic put a spotlight on the immune system, revealing there is still much about how it functions that is not well understood: Why do some people get severe disease and others don’t? And why can certain factors like age, or comorbidities like obesity, cause the immune system to go haywire?

University of Kentucky College of Medicine researcher Ilhem Messaoudi, Ph.D., has dedicated her career to answering these questions.

As an immunologist, Messaoudi’s research gives scientists a better understanding of how the immune system works, paving the way for improving how people respond to vaccines and infections.

“When it comes to immune responses, there is a sweet spot. Too little and the pathogen wins... too much and there is too much damage. As we’ve seen with COVID-19, an exuberant immune response might even be worse,” said Messaoudi. “I’m very interested in things that disrupt the proper function of the immune system because they can reveal more about how it works.”

Appointed chair of the Department of Microbiology, Immunology and Molecular Genetics in November, Messaoudi leads a team of microbiologists and immunologists who study pathogens and our bodies’ responses to them.

Most recently at the University of California, Irvine, Messaoudi brings an expansive research portfolio to UK. Current projects in Messaoudi’s lab include studies examining the impacts of alcohol abuse, obesity and aging on the immune system. Her work also includes research on what makes certain pathogens cause the immune system to function poorly and cause prolonged disease.

Another focus of the Messaoudi lab is the maternal immune system, and the delicate balancing act it must perform in order to maintain that “sweet spot” during pregnancy.

“The immune system of the mother has to undergo this massive transformation for nine months to facilitate implantation and promote the growth of a fetus, all while protecting both from microbial attacks,” Messaoudi said. “The immune response is dampened so the body does not reject the fetus, but not so much that it will put the mother or the fetus at jeopardy of getting an infection. What are the changes that take place in the maternal immune system to make this happen?”

Messaoudi’s research is focused on those changes and factors that can interfere with them, which can be detrimental to a pregnancy. She is currently working on two studies supported by the National Institute of Allergy and Infectious Diseases that focus on the impacts of maternal obesity on immune function of the mother and baby.

The studies are giving insight as to why women with a high pre-pregnancy body mass index and babies born to them have reduced immune function, making them more susceptible to severe disease.

Messaoudi’s research found that immune cells in the umbilical cord blood of babies born to mothers with obesity had DNA that was modified differently. Findings also show that mothers with obesity have increased inflammation in the placenta, which causes immune cells to “shut down” to avoid exacerbating the condition.

Messaoudi says the findings will help frame early interventions targeting maternal obesity, as well as future studies looking at how it could impact children later in life.

“The rates of obesity amongst women of childbearing age have increased at an alarming rate, making it one of the most common comorbidities during pregnancy,” Messaoudi said. “There's a lot of interest in understanding how maternal obesity impacts maternal-fetal health, but very few studies have dissected this question at the level of the cord blood, the placenta, and the mom. I think we're really helping the field of maternal-fetal health grow.”

And like so many other researchers during the pandemic, Messaoudi has also shifted the focus of her work to address COVID-19. Her lab has studied how SARS-CoV-2 infection during pregnancy impacts the maternal and fetal immune systems. Adding to more knowledge, which she says the pandemic has brought to the field of immunology.

“There are still many unanswered questions, but because we’ve diverted so many resources into understanding this one pathogen, we now understand so much more about the immune system than we did just two years ago.”

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers R01AI142841 and R01AI145910. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.