Disease processes in multiple sclerosis (MS) likely contribute to the increased sensitivity to airway infections seen in MS patients, a series of experiments in mice demonstrated.
The study, presented at the ACTRIMS 2017 Forum, showed that suppressive immune cells travel to the lungs and prevent an essential inflammatory reaction to viral infection. MS patients are known to die of infections like influenza four times more often than healthy people.
Titled “Induction of CNS-targeted autoimmunity leads to increased influenza mortality in mice,” the study was presented by Dr. Justin Glenn, of Johns Hopkins University School of Medicine, at the Young Investigator Platform Presentations Session on Feb. 23, the forum’s first day.
Glenn and colleagues figured that an immune response that targets the brain and spinal cord somehow changes the lung environment, leaving MS patients less resistant to infections such as influenza (the flu virus).
They used a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) mouse — to test this idea, infecting the animals with a mouse-adapted strain of the H1N1 influenza virus. The dose was adjusted to make sure mice would not die from the viral infection itself.
As predicted, normal mice with influenza survived, as did mice with EAE but without airway infection. But only 30 percent of the mice with both EAE and influenza infection survived.
The team next analyzed the lungs and tracked immune responses in the animals. They discovered that EAE prevented early inflammatory responses that are part of the innate immune system — the first line of defense against infections. Later immune responses, involving a specific type of T-cells, were also affected.
Investigating further, the team noted that EAE triggered the migration of a suppressive immune cell type into the lungs, where these cells suppressed the immune T-cell responses and prevented other factors, also involved in the inflammatory response, from doing their job.
Researchers also noted that the suppression of T-cells involved increased production of nitric oxide, which could be prevented by blocking the enzyme responsible for the production of this gas.
Studies have shown that the increased morbidity and mortality in airway infections among MS patients is not linked to the use of immunosuppressant medications. These findings may help to explain why, and offer researchers new opportunities to search for treatments against this process.
The ACTRIMS 2017 Forum is taking place Feb. 23-25 in Orlando, Florida.