Mycobacterium avium complex (MAC) bacteria can be found everywhere, so almost everyone breathes some of it in occasionally. While these microbes are related to deadly Mycobacterium tuberculosis, MAC tends to be harmless, existing in soil, water, dust, or even food without causing problems for most people. But sometimes, the opportunistic MAC makes someone very ill. MAC can take advantage when a person has risk factors like a structural lung disease or cystic fibrosis that make illness from MAC infections more likely, noted Cecilia Lindestam Arlehamn, Ph.D., Research Assistant Professor at La Jolla Institute for Immunology (LJI).
For the first time, researchers in the Lindestam Arlehamn laboratory have now revealed one reason why some people get so sick from MAC. They identified a defect in immune cells, which causes a reduction in the levels of specialized Th1* (Th1 star) cells. People who do not produce enough Th1* cells cannot effectively attack MAC bacteria, and they develop an illness. The findings have been reported in Frontiers in Immunology, and they could help create biomarkers that identify those at risk, or ways to treat the infection.
"We think these people have this cellular defect going into MAC exposure," explained Lindestam Arlehamn.
While T cells are normally the ones that respond to an infection, work by Lindestam Arlehamn and colleagues showed that T cells have only a limited response to a MAC infection, which is very unusual.
But this research did highlight a problem that might be to blame for MAC infection illness in some people. There were significant differences in gene expression in people who had previously had an active, symptomatic MAC infection compared to healthy individuals. People who had experienced MAC illness also carried an immunological defect leading to low Th1* cell levels. Normally, Th1* cells can alert the body to danger posed by a pathogen.
The Th1* defect seems to leave carriers vulnerable to disease. The researchers suggested that when there are not enough Th1* cells, some other crucial immune cells are never alerted about the MAC invasion, and an immune response is not activated. So people susceptible to MAC infection may have innate immunity that is overly responsive, while the adaptive response is not adequate, suggested the researchers.
In individuals with other conditions, such as cystic fibrosis, the burden is too high to overcome. Thick mucus in the lungs could impede T cells' ability to detect and attack MAC, while the lack of Th1* cells causes additional weakening of the immune response.
Now, the researchers want to confirm that people with fewer Th1* cells had the cellular defect before their MAC infection happened, as well as comparing people in a shared environment who were exposed to the same MAC, to look for differences in how T cells respond. Scientists want to solve the mystery of how MAC goes from harmless to harmful.