Advances in HIV treatment have dramatically improved patient lifespans and quality of life, yet nagging side effects remain—particularly chronic inflammation, as the imbalance in the immune system causes the body to attack itself. Case Western Reserve University is focusing on the mouth and throat, where inflammation can be especially harmful to patient health, as it has been linked with oral cancer, lesions, viral infections, and other ailments that can make eating painful and further weaken immune systems through malnourishment.
“Restoring balance to an immune system is key after being altered by HIV and medications,” said Pushpa Pandiyan, PhD, assistant professor of biological sciences at the Case Western Reserve School of Dental Medicine. She will lead the research with a 5-year, $1.59 million grant from the National Institutes of Health. “Otherwise, a person’s natural defenses can sometimes be too aggressive, especially in vulnerable areas like the gums and other oral tissues. Eventually, our findings could have the potential to help HIV patients lead even healthier, longer lives.”
Currently, more than one third of HIV patients develop oral conditions from immune systems compromised by HIV and its treatment. In battling HIV, some immune cells fare better than others, especially when interacting with the disease’s treatments. The researchers will focus on better understanding certain white blood cells called regulatory T-cells or “Tregs,” which help an immune system direct an appropriate response. Specifically, they will investigate how mechanisms within these cells—usually particular proteins among millions of their kind—can go haywire, resulting in too few or too many of certain Tregs.
The researchers hope to discover ways to replenish these beneficial white blood cells while reducing those that are dysfunctional. For instance, some pathogens can manipulate Tregs into prolonging inflammation—so-called “turncoat cells”—that can damage tissues, as Pandiyan found in previous research. By studying oral and throat tissues from HIV-positive patients taking common antiretroviral drugs to treat the disease, the researchers hope to pinpoint the origin of cells they suspect may promote inflammation or, at a minimum, don’t battle it.
The knowledge could lead to new ways to fight HIV-related diseases, Pandiyan said, in part by building on some of her previous findings. In 2014, her lab showed how specific T-cells can be manipulated outside the body to boost or suppress proteins that help the cells’ survival, which then can be re-inserted to help balance immune responses.
“Our bodies have many fine-tuned switches that keep defenses optimal,” Pandiyan said. “The more we understand the mechanisms of these switches, and how they behave under a variety of circumstances, the better we can control them to improve health.”
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