Discovery of a rapid immune response to a dangerous skin infection

2021

Challenge

Human skin and mucus membranes are inhabited by a plethora of bacteria. Many are beneficial, but some are dangerous when they penetrate the skin. Among potentially harmful skin-colonizing bacteria, Staphylococcus aureus is the most significant in terms of infection severity and frequency. Prevailing thought is that skin cells initiate an immune response within the bloodstream after encountering structures present on the surfaces of many different bacteria. It remains poorly understood, however, how human immune defenses distinguish between more and less harmful bacteria and mount an efficient immune response to prevent development of an infection from a threat as dangerous as S. aureus.

Advance

IRP investigators led by Michael Otto, Ph.D., used imaging of S. aureus skin infections in mice to reveal that toxins called PSMs, which are secreted by S. aureus, stimulated an immune response that considerably preceded initiation of a more general immune response within skin cells. They demonstrated that S. aureus PSMs directly attract immune cells called leukocytes from the bloodstream after the bacteria invade the skin, and this attraction is mediated by a protein called EGR1 in the leukocytes. This means that rather than leukocytes having to wait in the bloodstream for skin cells to send an alarm, leukocytes themselves have a surveillance shortcut specific to S. aureus that precedes skin cells’ response to the bacteria by several hours.

Impact

Swift recruitment of leukocytes is critical in preventing infection when bacteria breach through the protective layers of the skin. Discovery of this rapid immune response to a specific strain of bacteria reveals a new facet of the immune system and suggests that other specialized immune responses may exist. These mechanisms provide compelling new targets for the development of novel therapeutics and measures to prevent infection, which are critically needed as bacteria become increasingly resistant to currently used antibiotics.

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