Background

Mucosal Immunology Studies Team

The mucosal epithelium, with a combined surface area more than 100 times larger than skin, is both an initial barrier to pathogen entry and the primary site of entry for many pathogens (e.g. influenza virus, human immunodeficiency virus, herpes simplex virus, enterotoxigenic Escherichia coli, Vibrio cholerae). Since most pathogens first contact the host through the mucosal surface, and efficient person-to person transmission of many pathogens results from an initial mucosal infection, development of vaccines and therapies that target and protect mucosal surfaces would be a significant achievement. Despite several successes in mucosal vaccination (e.g. oral polio vaccine, FluMist, RotaRix, oral cholera vaccine), and substantial research devoted to mucosal vaccine development, the critical elements required for protective mucosal immunity are not well understood.

The mucosal immune system must satisfy a range of diverse requirements from maintaining sterility in the lungs and upper reproductive tract to coexisting with numerous species of commensal bacteria in the colon. An imbalanced mucosal immune response to food, to the normal microbial flora, or even to pathogens can lead to chronic inflammation and possibly death, so responses at the mucosa require tight controls. Recent studies have provided new clues about the strategies and cellular and molecular components used at different mucosal surfaces to detect and respond to pathogens without causing chronic inflammation, but much remains unknown.

In January 2008, the NIAID sponsored a workshop to discuss recent research advances in mucosal immune defense mechanisms. The workshop participants concluded that multiple gaps exist in the understanding of the basic immune mechanisms responsible for induction of broad systemic and mucosal immunity, priming, protection, and tolerance. These gaps hamper progress in developing therapeutic and vaccination strategies to provide mucosal and systemic protection from mucosal pathogens and inflammatory diseases. This led to RFA AI-10-008 "Immune Defense Mechanisms at the Mucosa Cooperative Study Group (U01)" which supported a cooperative program to address these research gaps. At the first Steering Committee meeting held in January 2012, the group adopted the name "Mucosal Immunology Studies Team (MIST)". The U01 was renewed in 2022 and is currently administered by Drs David Artis and Gregory Sonnenberg at Weill Cornell Medicine in New York City.

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Background
Project Investigators

Photo: Scanning electron microscopy image colorized to demonstrate the interactions between uropathogenic E. coli (pink), the epithelium (blue), and the innate immune system (yellow) at the urinary bladder mucosal surface in a mouse model of urinary tract infection. Photo Credit: Hultgren laboratory and the Center for Cellular Imaging (WUCCI), Washington University in St. Louis.