A team of US researchers on Wednesday said they have found a rare mutation that leaves its carriers much more likely to become ill with tuberculosis (TB) — but, curiously, not with other infectious diseases.The research from The Rockefeller University in the US, published in the journal Nature, may upend long held assumptions about the immune system.
It has long been known that an acquired deficiency of a pro-inflammatory cytokine called TNF is linked to an increased risk of developing TB.
The current study, led by Rockefeller’s Stephanie Boisson-Dupuis and Jean-Laurent Casanova, revealed a genetic cause of TNF deficiency, as well as the underlying mechanism — a lack of TNF incapacitates a specific immune process in the lungs, leading to severe — but surprisingly targeted — illness.
The findings suggest that TNF, long considered a key galvanizer of the immune response, might actually play a much narrower role—a discovery with far-reaching clinical implications.
“The past 40 years of scientific literature have attributed a wide variety of pro-inflammatory functions to TNF,” says Casanova. “But beyond protecting the lungs against TB, it may have a limited role in inflammation and immunity.”
Over the years, the team has identified several rare genetic mutations that render some people vulnerable to TB.
For example, mutations in a gene called CYBB can disable an immune mechanism called the respiratory burst, which produces chemicals called reactive oxygen species (ROS). Despite its pulmonary-sounding name, the respiratory burst takes place in immune cells throughout the body.