A new study reveals an important and newly discovered pathway used by disease-causing bacteria to evade the host immune system and survive and grow within the very cells meant to destroy them. This discovery may lead to new treatments and vaccines for tuberculosis (TB) and certain other chronic bacterial and parasitic infections.
The research, supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the work of the laboratories headed by Peter Murray, Ph.D., at St. Jude Children's Research Hospital in Memphis, Tenn., and Thomas Wynn, Ph.D., of the Laboratory of Parasitic Diseases at NIAID. Their findings appear in the November issue of Nature Immunology.
Clearing the body of disease-causing bacteria is the job of specialized white blood cells called macrophages. The word "macrophage" means "big eater" in Latin and that is just what these cells are - they gobble up cell debris, infected cells and disease-causing bacteria found in the body. To help them digest and destroy what they eat, macrophages make compounds that in most cases kill pathogens. One of these chemicals is the free radical nitric oxide (NO).
However, some harmful bacteria, known as intracellular pathogens, live inside cells and can even survive and replicate within macrophages, somehow inhibiting or escaping killing by NO. One natural NO inhibitor made by macrophages is the enzyme arginase. Arginase steals and degrades the material required to make NO, therefore limiting how much NO is made.
"The bacteria designed to live inside the cell are highly adapted to their environment," says Dr. Murray. "We wanted to determine just how intracellular bacteria were turning on the genes that make arginase, thereby controlling the expression of NO and escaping killing by macrophages."
The research team discovered that intracellular pathogens increase levels of arginase, thereby reducing the amount of NO the macrophages produce, enabling intracellular pathogens to survive. The presence of persistent intracellular bacteria is particularly harmful to people with compromised immune systems, such as people with HIV or cancer, who often contract chronic bacterial and parasitic infections.