Some people may be susceptible to uncommon bacterial illness because of immune deficiency
ANI Oct 05, 2022
Everybody occasionally breathes in Mycobacterium avium complex (MAC) bacteria, yet the majority of individuals don't become ill.
These dangerous Mycobacterium tuberculosis cousins usually spend their brief, innocuous lives in food, soil, water, or dust. Then there are those uncommon individuals who become extremely ill. According to Cecilia Lindestam Arlehamn, PhD, research assistant professor at La Jolla Institute for Immunology, MAC is an "opportunistic" pathogen (LJI).
Some persons do have risk factors that increase their likelihood of experiencing symptoms after being exposed to MAC, including cystic fibrosis and structural lung problems. The issue is that no one is entirely certain as to why these variables varied so significantly.
The risk of acquiring MAC illness has now been linked to an immune cell abnormality discovered in Lindestam Arlehamn's lab. Her team found that individuals with signs of MAC infection have less specialised Th1* (Th1 "star") cells, which prevents them from mounting a successful immune response against the germs.
Lindestam Arlehamn, who closely collaborated on the study with associates at the University of Washington, said "We think these people have this cellular malfunction coming into MAC exposure."
This study could be a first step in identifying biomarkers that can predict MAC disease patients' likelihood of developing progressive lung illness and their treatment responses.
When T cells don't fight back
Lindestam Arlehamn studied how T cells combat the illness. She hoped to find critical sites, or epitopes, where MAC-infected cells are vulnerable to immune system attacks by examining T cells from individuals who had previously contracted MAC.
To everyone's amazement, Lindestam Arlehamn's research showed that the human body has a very limited T cell response to MAC infection and that she was unable to identify MAC-specific epitopes. T cells are often essential for fighting infections.
A T cell response to a pathogen being so restricted is quite uncommon. It appeared as though the trial participants who contracted MAC had little to no "immune memory" of contracting the illness. Instead, the SPARK research by Lindestam Arlehamn revealed an unanticipated cellular flaw that might help to explain why some people get sick while others don't. Lindestam Arlehamn adds, "This was also quite interesting."
The hidden culprit
Lindestam Arlehamn observed a striking difference between blood samples from persons who had previously been infected with MAC and healthy controls when she examined global gene expression (which genes are "turned on") in response to MAC infection.
People with MAC looked to have an immunologic abnormality that causes their bodies to have less specific "helper" immune cells known as Th1* cells. Normally, Th1* cells aid in warning the body's pathogen-fighting cells of danger.
The Th1* cells are especially important for fending off a Mycobacterium attack, whether it comes from MAC or Mycobacterium tuberculosis, according to Lindestam Arlehamn and her colleagues, who were among the first to demonstrate this.
The first evidence that this Th1* deficiency can raise disease vulnerability comes from their work. They believe it is likely that without sufficient Th1* cells, some important immune cells would never learn that MAC is attempting to intrude.
This indicates that MAC-susceptible individuals may have both an underperforming adaptive immune response as well as an overactive innate immune response (with specific cells causing inflammation early in the illness phase) (a lack of activated T cells to actually stop the disease).
This loss of immunological protection is intolerable for some people. Thick lung mucus, for instance, may make it difficult for T cells to patrol the tissue and find MAC in persons with cystic fibrosis. Therefore, a deficiency in Th1* cells could deal a double blow to the lungs' already frail immune system by causing immune system malfunction. That may help to explain it, according to Lindestam Arlehamn.
Next steps for fighting MAC
Lindestam Arlehamn is currently trying to determine whether the deficiency that results in fewer Th1* cells is present in persons even before they are exposed to MAC. To determine whether a lack of Th1* is also a characteristic for those who have the disease early in its course, she intends to examine samples taken from patients. Additionally, she would like to examine blood samples from individuals who had contact with the same MAC environmental sources.
"It's likely that you are exposed too if you live with someone who has MAC illness," she explains. Looking for differences between those who become sick and those who don't, we want to see whether we can identify unique T cell responses in those people.
This discovery may aid in understanding how MAC transforms from a benign to a highly pathogenic state.
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