Washington : Scientists have found out how disease-causing bacteria evade the host’s immune system, even surviving and growing within the very cells meant to destroy them. This discovery may open the way 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), is the work of Peter Murray, St. Jude Children’s Research Hospital, Memphis, and Thomas Wynn, Lab of Parasitic Diseases at NIAID.
Clearing the body of disease-causing bacteria is the job of specialised white blood cells (WBCs) 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,” said 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, according to an NIAID release. These findings appear in the November issue of Nature Immunology.
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.
“Although NO was named ‘molecule of the year’ in 1992 by Science Magazine and studied as an important part of the immune response to bacterial infections, arginase, its counterbalance, was widely ignored by the immunology community,” informed Wynn. “This work suggests that targeting arginase may be helpful in treating chronic, intracellular bacterial and parasitic infections.”