NIAID Scientists Identify New, Rapid Response to Bacterial Skin Infection

NIAID Scientists Identify New, Rapid Response to Bacterial Skin Infection

When bacteria infect the skin, structures on the bacterial surface that are common to all bacteria stimulate our immune system to respond. A new study in mice from NIAID scientists now shows that toxins from Staphylococcus aureus alarm the immune system hours earlier than previously known. The unanticipated findings, which identify a new immune signaling mechanism for infection control, has greatly expanded researchers’ knowledge about early host-pathogen interaction.

The study, published Dec. 6 in Nature Microbiology, began nearly 15 years ago shortly after the laboratory of Michael Otto, Ph.D., discovered phenol-soluble modulins (PSMs), a type of staphylococcal toxin. The new work involved the scientists monitoring the length of time for neutrophils to travel to the site of infection. Neutrophils are the primary tool the immune system uses to destroy invading bacteria.

Using a special type of microscope to observe cells in live mice, the scientists realized that the neutrophil response in mice infected with S. aureus lacking PSMs was delayed by several hours compared to the response in mice infected with natural S. aureus. S. aureus is the most common cause of skin infections in the United States; the bacterium is highly resistant to antibiotic treatment and can lead to secondary lung infection and death.

The delay in neutrophil response made the scientists realize that the immune system recognizes the PSMs as an early signal for an S. aureus invasion. They subsequently learned, to their astonishment, that the neutrophils were responding from the bloodstream, not due to bacterial interaction with skin cells, which is the common thinking. They also identified the internal signaling mechanism of how neutrophils respond to PSMs.

The researchers say these findings suggest that the type of bacteria involved in an infection determines the speed and intensity of the immune response – much more than previously thought. PSMs, which are specific for staphylococci, may only represent one example of a danger signal that the immune system senses. Similar signals in other harmful bacteria remain to identified. 

Reference: T Nguyen, et al. Rapid pathogen-specific recruitment of immune effector cells in the skin by secreted toxins. Nature Microbiology DOI: https://doi.org/10.1038/s41564-021-01012-9 (2021).