Gamma delta T cells may hold key to preventing staph infection recurrence


New insights into how the human immune system protects against recurrent staphylococcus aureus skin infections may lead to the future development of vaccines against skin staph infections.

Researchers from Johns Hopkins University in Baltimore, the University of California, Davis, and the U.S. National Institute of Allergy and Infectious Diseases published these findings online in The Journal of Clinical Investigation on Feb. 5, 2018.

“There’s a huge, unmet clinical need for new approaches against staph skin infections because of declining antibiotic development and rising drug resistance,” said senior author Dr. Lloyd Miller, associate professor of dermatology at Johns Hopkins University School of Medicine, in a press release. “There are concerns that current antibiotics will not provide a durable solution to this public health threat.”

Staph infections are responsible for 14 million outpatient visits, nearly 500,000 hospital admissions and US$3 billion to $4 billion in inpatient health care costs in the U.S. per year, according to the release. Once someone has had a staph infection, there is a 50% recurrence rate within six months.

Studying mice bred to have defective immune systems, Dr. Miller’s research team found that after an initial exposure of the skin to staph, the mice were unexpectedly protected against a second skin exposure with the same bacteria. After testing for antibodies and other immune markers of response against this infection, the researchers were not able to clearly identify what immune response was protecting the mice. They then tested in the mice a medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple sclerosis, which acts by preventing certain immune cells from leaving lymph nodes for sites of inflammation.

“We couldn’t have figured out what was happening without the expertise of our collaborators at UC Davis, who determined the genetic sequence of every single cell marker on the cells in the lymph nodes,” says Dr. Miller.

The genetic sequencing data revealed that certain specific immune cells—gamma delta T cells—multiplied significantly after the initial staph infection and moved through the skin to the infection site, providing protection against subsequent infections. Accounting for less than 1% of all cells in the lymph nodes prior to infection, post-infection the gamma delta T cells accounted for more than 20% of the cells in the nodes.

To determine if the mouse model results were applicable to humans, the research team collaborated with investigators from the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to test blood from healthy individuals and people with a rare immune disorder that makes them highly susceptible to staph skin infections—IRAK4 deficiency.

According to Dr. Miller, half of people with the deficiency die by age 10. However, those that survive to adulthood overcome their susceptibility to staph infections. In blood samples from these patients, the researchers found an increase in the percentage of gamma delta T cells, similar to what they observed in mice, which remained stable over years.

“This was a totally unexpected result,” said Dr. Miller. “We are excited to learn more about these cells and how they confer this long-lasting protective immunity.”

In the release, Dr. Miller noted he hopes these new findings will aid in the development of new therapies or even a vaccine against staph skin infections, possibly through direct targeting of gamma delta T cells. Having new, targeted therapies could alleviate the burden of staph skin infections, prevent invasive complications, and reduce healthcare costs, he said.

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