Landmark study points to source of rapid aging, chronic inflammation in
people living with HIV

Date:
November 9, 2021
Source:
University of Alberta Faculty of Medicine & Dentistry
Summary:
In a groundbreaking study of people living with HIV, researchers
found that elusive white blood cells called neutrophils play a role
in impaired T cell functions and counts, as well as the associated
chronic inflammation that is common with the virus.



FULL STORY ==========================================================================
In a groundbreaking study of people living with HIV, University of Alberta researchers found that elusive white blood cells called neutrophils play
a role in impaired T cell functions and counts, as well as the associated chronic inflammation that is common with the virus.


========================================================================== Neutrophils are a foundational part of the body's immune system and the
most abundant type of white blood cell, making up about 60 to 80 per cent
of circulating immune cells in the blood. However, unlike other types
of white blood cells, neutrophils are extremely short-lived and cannot
be frozen and thawed like other immune cells, making them extremely
difficult to examine, said study lead Shokrollah Elahi.

"Neutrophils live for hours to a day or two maximum," Elahi 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." In the study, published in the journal PLOS Biology,Elahi
and his team examined the fresh blood of 116 people living with HIV and
60 individuals without the virus. They ran comprehensive sequencing on
all the genes expressed in the neutrophils from both groups to determine
any differences between them.

"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." Elahi, a member of
the Women and Children's Health Research Institute, the Cancer Research Institute of Northern Alberta and the Li Ka Shing Institute of Virology,
said neutrophils act like an early alarm system. When they detect a
dangerous entity such as an invading microbe, they release proteins to
signal other immune cells to the danger. This activation can be high
or low, or more or less potent, depending on the severity of the danger
and the reaction of other immune cells.



==========================================================================
One of the proteins released by neutrophils is galectin-9, which Elahi previously linked to severe inflammation and cytokine storms in COVID-19 patients. Elahi's team reported that when neutrophils sense a danger
such as an infection, they become stressed and release the galectin-9. As
the protein begins to saturate the blood, it can interact with different
immune cells. For example, the team found that galectin-9 reacted strongly
with T cells and made them more susceptible to HIV infection, causing
a cascading effect that leads to a hyper-immune response and inflammation.

Elahi's prior work showed that patients with HIV and some forms of cancer showed elevated levels of galectin-9 in their blood. However, in this
latest study he was able to identify the major source of the protein.

"We found for the very first time that the neutrophil membrane, through
a complex mechanism, is covered like a blanket with galectin-9,"
he said. "When neutrophils become highly activated, the secretion of
galectin-9 can activate T cells through interaction with another molecule called CD44, which then promotes chronic inflammation in HIV patients."
Elahi's study of neutrophils revealed that the "alarm" reaction of
shedding proteins such as galectin-9 was associated with oxidative
stress, a state in which the body is unable to naturally detoxify or
remove certain oxygen- containing molecules that become harmful to
cells. Oxidative stress is believed to play a role in the development
of diseases including Parkinson's, Alzheimer's, cancer, heart failure
and autism.

Based on his findings, Elahi said preventing galectin-9 shedding might
be a powerful tool in reducing many of the negative effects of HIV
infection. His team has already made some progress in reducing oxidative
stress by using an organic antioxidant compound called phloretin and
vitamin C.

"We have been looking at phloretin and vitamin C in the lab and our data
are very promising," Elahi said. "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."
Elahi noted the study reinforces that the most important thing for people
who are living with HIV or are at risk of catching the virus is to get
a screening test as soon as possible.

"If the virus is caught early and they can go on
antiretroviral therapy, then it stops disease progression and
reduces many of the complications associated with advanced HIV." ========================================================================== Story Source: Materials provided by University_of_Alberta_Faculty_of_Medicine_&_Dentistry.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Garett Dunsmore, Eliana Perez Rosero, Shima Shahbaz, Deanna
M. Santer,
Juan Jovel, Paige Lacy, Stan Houston, Shokrollah Elahi. Neutrophils
promote T-cell activation through the regulated release
of CD44-bound Galectin-9 from the cell surface during
HIV infection. PLOS Biology, 2021; 19 (8): e3001387 DOI:
10.1371/journal.pbio.3001387 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211109155142.htm

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