Commensal Bacteria Found to Regulate Immune Cells in Lungs to Produce Proteins Critical for Host Defense
Microbiota—the trillions of bacteria that co-exist in the body—regulate the ability of lung dendritic cells to generate immune responses, according to a study led by researchers from the Icahn School of Medicine at Mount Sinai, published online in the Journal of Experimental Medicine.
“Our findings demonstrate a clear role of bacteria in modulating immune function in the lungs, which were long considered ‘sterile’ sites,” said Saurabh Mehandru, MD, senior author of the paper and Assistant Professor of Medicine in Gastroenterology, Icahn School of Medicine at Mount Sinai. “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 contains approximately ten times as many bacterial cells as human cells. Known as commensal bacteria, they exist in a mutually beneficial, symbiotic relationship with their human hosts, helping with a diverse range of functions that are only beginning to be understood. While a majority of previous studies have focused on how bacteria shape and protect the immune system within the intestines, it is becoming clear that other sites of the body also benefit immensely from commensal bacteria.
The immune system produces a complex range of proteins and chemicals to protect against infections, allergies and cancer. One group of these proteins is called immunoglobulins, or antibodies, that are produced by specialized cells called B cells. Immunoglobulin A (IgA) is the predominant antibody within the inner lining of the body, called the mucosa; intestines and lungs are two of the largest mucosal surfaces. At these sites, IgA is shown to protect against infections. Evidence is also emerging that IgA may help suppress allergies at these sites.
To study the production of IgA within the lungs, the researchers used mouse models to isolate specialized cells called dendritic cells and cultured them with antibody-producing B cells. After four to five days of culture, the B cells started producing the IgA antibody in a process called “IgA class switch recombination.” To the researchers’ surprise, they found that when they isolated lung dendritic cells from “germ free” or antibiotic-treated mice, the production of IgA was highly impaired. Further, when the germ-free mice were fed with a component of bacterial cell wall called LPS, the lung dendritic cells started instructing B cells to produce IgA again.
Indiscriminate use of antibiotics in clinical use as well as in food production in western countries has changed the bacterial composition of our body, causing dysbiosis (microbial imbalance), and coinciding with a dramatic increase in allergic disorders like asthma and food allergies. With this study, Mount Sinai researchers have shown a key link between antibiotic use, dysbiosis and reduced production of IgA within the lungs. Since low levels of IgA have previously been shown to relate to asthma and other allergic diseases, this in turn provides a novel mechanism behind the rising incidence of these disorders in the western populations.
Additionally, researchers have shown that changing the bacterial composition of the body may have important consequences on the effectiveness of vaccines used to protect the mucosal surfaces of the body against infection. Thus, their study demonstrates how commensal bacteria may affect important aspects of lung immunity, in turn increasing our susceptibility to allergies and infections.
This work was supported by grants from the American Gastroenterology Association Elsevier Award and The National Institutes of Health/National Center for Research Resources.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system encompassing (with the addition of South Nassau Communities Hospital) eight hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.