Gut Microbiome Regulates Key Immune Responses in the Lungs

Gut Microbiome Regulates Key Immune Responses in the Lungs

Researchers from the Icahn School of Medicine at Mount Sinai in New York recently showed that the microbiome, a bacteria that lives in our gut, also regulates the responses of immune cells in the lungs, impacting the body’s ability to protect itself against infections.

The study, entitled “Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses,” was published in the Journal of Experimental Medicine.

The human microbiome outcompetes the number of human cells by a factor of 10, and recent findings show that these commensal, symbiotic bacteria are actually vital for the healthy functioning of our bodies. While the first studies focused on the role of the microbiome in our gut, the bacteria is increasingly being recognized for its impact on other parts of the body. The Icahn medical school researchers are showing how the microbiome regulates immune cell responses in the lungs.

Antibodies, also known as immunoglobulins, are produced by cells of the immune system (B cells) to protect us against infections, allergies and cancer. Immunoglobulin A (IgA) is the main type produced within the epithelium layer lining the body, called mucosa, with the intestine and lungs being the major mucosal surfaces. Researchers investigated how the microbiome may impact the protective IgA responses orchestrated by another type of immune cells, the dendritic cells, but this time they looked at the lungs.

Researchers isolated dendritic cells and cultured them with antibody-producing B cells. Within five days of culture, the B cells started producing the IgA antibody. Notably, when the team used two different mouse models to mimic a no-microbiome condition, either “germ-free” mice or antibiotic-treated mice, and extracted their dendritic cells, they found that in cultures with B cells, the production of IgA was highly impaired. And feeding the germ-free mice with LPS (a component of the bacteria cell wall) offered another surprise: The lungs’ dendritic cells began inducing B cells to produce IgA again.

“Our findings demonstrate a clear role of bacteria in modulating immune function in the lungs, which were long considered ‘sterile’ sites. 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,” concluded Saurabh Mehandru, MD, the study’s lead author and an assistant professor of medicine in gastroenterology at the Icahn School of Medicine, in a press release.

These findings help explain why low levels of IgA have been associated with asthma and other allergic diseases, and why the indiscriminate use of antibiotics in western countries changes the bacterial composition of our bodies, leading to a dramatic increase in these type of diseases. Moreover, the research shows how altering our microbiome composition may also impact the effectiveness of vaccines against infectious agents, particularly in the mucosal surfaces of our bodies.

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