Researchers have discovered how the immune system might protect a person from recurrent bacterial skin infections caused by Staphylococcus aureus (staph). The findings, publishing online this week in The Journal of Clinical Investigation, provides new opportunities to developing vaccines to prevent staph skin infections, which account for 14 million outpatient visits, nearly 500,000 hospital admissions and $3 billion to $4 billion in inpatient health care costs in the U.S. per year. Research team included experts from Johns Hopkins, the University of California, Davis, and the National Institute of Allergy and Infectious Diseases.
Using mice with defective immune systems, research team found that after an initial exposure of the skin to staph, they were surprisingly protected against a second skin exposure with the same bacteria. After testing for antibodies and other “usual suspects” of the immune system against this infection, it was not at all clear what immune response was protecting the mice. The researchers then tested a drug FDA-approved for treatment of multiple sclerosis, which acts by preventing certain immune cells from leaving lymph nodes for sites of inflammation. Researchers then sequenced genes of every cell line in lymph nodes.
That genetic sequencing data revealed that specific cells substantially multiplied after the initial infection, then moved to the infection site and provided protection against the second infection. These so-called gamma delta T cells account for less than 1 percent of all the cells in the lymph node prior to infection. After infection, they accounted for more than 20 percent.
Since this work was performed in mice, the team wanted to see if its findings were applicable to people. Working with collaborators from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, the researchers tested blood from healthy individuals and people with a rare immune disorder that makes them highly susceptible to staph skin infections.
According to Lloyd Miller, M.D., Ph.D., associate professor of dermatology at the Johns Hopkins University School of Medicine, half of people with the disorder die by age 10, but if they survive to adulthood they somehow 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.
Miller hopes these new findings and especially gamma delta T cells may be targeted for developing new therapies or even a vaccine against staph skin infections. This, he says, could alleviate the burden of staph skin infections, prevent invasive complications and reduce health care costs.
Citation: Dillen, Carly A., Bret L. Pinsker, Alina I. Marusina, Alexander A. Merleev, Orly N. Farber, Haiyun Liu, Nathan K. Archer, Da B. Lee, Yu Wang, Roger V. Ortines, Steven K. Lee, Mark C. Marchitto, Shuting S. Cai, Alyssa G. Ashbaugh, Larissa S. May, Steven M. Holland, Alexandra F. Freeman, Loren G. Miller, Michael R. Yeaman, Scott I. Simon, Joshua D. Milner, Emanual Maverakis, and Lloyd S. Miller. “Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection.” Journal of Clinical Investigation, 2018. doi:10.1172/jci96481.
Funding: MedImmune, Regeneron, Moderna Therapeutics, Pfizer, National Institutes of Health, Burroughs Wellcome Fund.
Adapted from press release by John Hopkins Medicine.