Proof proper nutrition is essential to good health: Scientists explore how the immune system uses calcium to fight viral infections

Researchers at New York University School of Medicine, in a study that was published in the online journal Immunity, found that a calcium signal manages the immune cells’ ability to use the nutrients that are needed to boost their reproduction into a cellular army so as to drive away invading viruses.

The study findings focus on the wide-scale immune counterattack made by T cells (T lymphocytes) in response to viral infection. When this type of white blood cell is activated by an invader, it multiplies into an army of clones that are designed specifically to attack that invader.

According to the study, the ability of T cells to use energy from blood sugar (glucose) to reproduce is dependent on how calcium flows into cells, researchers say.

When they receive the right signal – the recognition of virus particles – T cells make a pathway in their outer membranes, allowing calcium to flow in to activate the protein NFAT (nuclear factor of activated T-cells), a transcription factor that turns on genes.

Furthermore, a particular type of calcium influx – store-operated calcium entry (SOCE) – manages the activation of NFAT and its ability to turn on genes that manage the uptake and breakdown of glucose.

“Our results argue that SOCE, in cooperation with the enzyme calcineurin, regulates the conversion of glucose into cellular energy and building blocks needed for T cell proliferation,” NYU School of Medicine pathology department’s experimental pathology program associate professor Stefan Feske, who is also the senior author of the study, says.

The study – particularly the finding that a calcium signal enables the immune system to do its job – is relevant, since two widely-used drugs in the market, cyclosporin A and tacrolimus, are found to suppress the immune system’s ability to negate the effects of autoimmunity and transplant rejection by hindering the enzyme calcineurin from activating NFAT.

“Based on these results, we will look closer in future experiments at how SOCE regulates the metabolism of immune cells during autoimmune diseases, as well as immune responses against cancer,” says co-first author Martin Vaeth, Ph.D., a postdoctoral researcher in Feske’s laboratory.

During SOCE, calcium goes into T cells through calcium release-activated channels (CRAC). According to the team, mice that lacked the genes to correctly build these channels were not that strong when it came to fighting viral infections.

When researchers artificially placed glucose-handling genes that were controlled by SOCE back into the T cells, the cells’ ability to reproduce and fight infection came back. (Related: Hot chocolate enhances memory, modulates immune cells.)

“These results are timely because the field is currently exploring whether a drug class called CRAC inhibitors can be used safely against autoimmune and inflammatory diseases in human patients, and our study fills in key details on some of the relevant mechanisms,” Vaeth adds.

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