In what’s being touted as a landmark study, University of Alberta researchers have discovered that a certain type of white blood cells play a role in impaired T cell functions and counts. They also play a part in rapid aging and the chronic inflammation that is common with HIV.
The elusive cells are called neutrophils. These white blood cells are the biggest number of all types of white blood cells. They kill and digest bacteria and fungi. Doing so aids the body in healing wounds and fighting infections.
According to the study’s lead author, Shokrollah Elahi, neutrophils are very short-lived. Unlike other immune cells, they cannot be frozen, which makes them difficult to study.
“Neutrophils live for hours to a day or two maximum,” said Elahi, Associate Professor in the Department of Dentistry & Dental Hygiene, said. “The body produces a lot of neutrophils, and they do their job and then they die and have to be regenerated in the bone marrow. But despite the fact that neutrophils are the most abundant white blood cells in the blood circulation, their role in the context of HIV has not been very well defined.”
The team examined the fresh blood of 116 people living with HIV and 60 people without the virus. Comprehensive sequencing was run on all the genes expressed in the neutrophils. This was done to determine any potential differences.
“We found that not all HIV-infected individuals have similar types of neutrophils,” said Elahi. “As the HIV disease progresses, neutrophils become more activated and more potent, and in turn activate the body’s T cells, which likely causes some of the problems associated with HIV infection such as inflammation and rapid aging.”
When the neutrophils get stressed they release the protein galectin-9. This protein can interact with different immune cells once it starts to saturate the blood. The team discovered, for example, that galectin-9 strongly reacted with T-cells. That made them more susceptible to HIV infection, which led to a rushing effect and then inflammation and a hyper-immune response. Elahi’s previous work showed that patients with HIV and some forms of cancer had elevated galectin-9 blood levels. The new study identified the protein’s major source.
The study showed that neutrophils have an “alarm” reaction when shedding proteins such as galectin-9. It is linked to oxidative stress, when the body cannot naturally remove certain oxygen-containing molecules that become harmful to cells. It’s thought that this is a factor in the development of Parkinson’s disease, Alzheimer’s disease, cancer, heart failure and autism.
The findings show that preventing galectin-9 shedding could be a powerful tool in reducing many of the negative effects of HIV infection.
“We have been looking at phloretin and vitamin C in the lab and our data are very promising,” Elahi said of the antioxidant compound and vitamin. “We know that both are good at reducing galectin-9 shedding, so we believe they can prevent the hyper-activation of neutrophils. We hope that our results will spark renewed investigation into the role of neutrophils in T cell activation in other acute and chronic conditions.”
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