Researchers at the University of California, San Diego School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences have revealed that group B Streptococcus (GBS), a bacterial pathogen that causes sepsis and meningitis in newborn infants, is able to shut down immune cell function in order to promote its own survival.
Their study, published online July 13 in the Journal of Experimental Medicine
, offers insight into GBS infection - information that may lead to new medical therapies for invasive infectious diseases that affect nearly 3,500 newborns in the United States each year.
The UC San Diego researchers describe how GBS fools the immune system into reducing production of antibiotic molecules. "We have discovered that the bacteria have evolved to use a trick we call 'molecular mimicry,'" said Victor Nizet, MD, UC San Diego professor of pediatrics and pharmacy. "Like a wolf in sheep's clothing, GBS can enter our body without activating the immune cells that are normally programmed to kill foreign invaders."
The findings represent a collaborative effort between the laboratories of senior authors Nizet and Ajit Varki, MD, distinguished professor of medicine and cellular and molecular medicine. Varki is also co-director of the UCSD Glycobiology Research and Training Center, where the investigators have been exploring the interaction of bacterial pathogens with the innate immune system. Their most recent focus has been on the special role of Siglecs (short for sialic acid binding Ig-like lectins), members of the immunoglobulin family of antibodies.
Siglecs sense a chemical structure known as sialic acid - a sugar molecule that is abundant on the surface of all human cells - and send signals that control the gene expression and function of immune cells. Many specialized Siglecs receptors send negative signals, recognizing sialic acids as "self." These signals help keep the immune cells turned off under baseline conditions, avoiding unnecessary inflammation in the absence of infection or injury. Earlier this year, in a manuscript published in the journal Blood, the same UC San Diego team demonstrated that GBS decorates its own surface with sialic acid, closely resembling human molecules, and is thus able to bind Siglecs on immune cells, shutting down the cells' normal functions.