Recent times have revealed remarkable discoveries about the microbiome – the bacteria that co-exist with and vastly outnumber the cells of our bodies. Most revelations have centered on gut bacteria – but now, a new study shows that the lungs are also home to bacteria that help regulate the immune system.
The study, led by researchers from the Icahn School of Medicine at Mount Sinai in New York, NY, is published in The Journal of Experimental Medicine.
Senior author Saurabh Mehandru, an assistant professor of medicine in gastroenterology, says they found bacteria have a clear role in regulating immune function in the lungs – a place in the body that was once thought to be sterile – and notes:
“This provides the basis to study other aspects of lung immune function that may be affected by microbial communities, and may also help with improving nasal vaccines used to protect against infections of the lung and elsewhere in the body.”
The human body is home to trillions of “friendly” bacteria – known as commensal bacteria – that exist in mutually beneficial relationships with their host. We are only beginning to understand the important role they play in health and disease.
While most previous studies have focused on how this relationship works in the digestive system, the new study looks at how bacteria in the lungs influence the immune system through specialized cells called dendritic cells.
Dendritic cells are tree-like cells that help to create and limit immunity. They patrol the interfaces between our bodies and the environment, for example, the mucosa – the tissue that lines various surfaces in the body – and seek out foreign invaders such as bacteria, viruses or dangerous toxins.
When they find an invader – at this point the invader is called an antigen – the dendritic cells break it down into smaller antigen fragments and display them on their cell surfaces.
Sporting their antigen fragments, the primed dendritic cells then travel to immune centers such as the lymph nodes or the spleen, where other specialized cells use the antigens to make antibodies to neutralize the invader.
One such group of antibodies is called immunoglobulins that are produced in specialized immune cells called B cells.
Immunoglobulin A (IgA) is the main immunoglobulin in the mucosa, and it plays a key role in protecting the two largest mucosal surfaces of the human body – the intestines and the lungs.
Emerging evidence also suggests IgA in these mucosal surfaces may help suppress allergies.
For their study, the team used mouse models. They isolated lung dendritic cells, cultured them with B cells and showed how – after 4-5 days – the B cells started producing IgA antibody in a process known as “IgA class switch recombination.”
But, to their surprise, when they tried to repeat the result with cells taken from mice treated with antibiotics so they were germ-free, hardly any IgA antibody was produced.
And, when they fed the germ-free mice a compound called LPS that is found in the walls of bacterial cells, and then isolated and cultured the mice’s dendritic cells with B cells, IgA production was restored.
Indiscriminate use of antibiotics for medicine and agriculture is interfering with the mutually beneficial relationship between humans and their microbiome, giving rise to the steep increases we are seeing in asthma and food allergies, note the researchers.
They also note how there is evidence that low levels of IgA are linked to asthma and other allergic disorders.
The researchers propose that by revealing an important link between antibiotic use, the breakdown in the body’s important relationship with the microbiome, and reduced production of IgA in the lungs, their study points to a new mechanism behind the rise in allergic disorders.
They also suggest that such disturbances in the microbiome may have important implications for the effectiveness of vaccines designed to protect against infection in mucosal surfaces, as they conclude in their study paper:
“Herein, we demonstrate an unexpected role of the microbiota in modulating the protective efficacy of intranasal vaccination through their effect on the IgA class-switching function of [lung dendritic cells].”
Meanwhile, Medical News Today recently learned of another study that suggests the immune system influences the evolution of gut bacteria. The findings provide evidence for one side of the theory that the rich diversity of bacteria in our gut is the result of the two systems co-evolving and working on each other.