Immunological Consequences of Antigen Sampling at Mucosal Surfaces

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About this Research Topic

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Background

The epithelia lining the mucosal surfaces of the body are continuously exposed to external materials, and entails the risk of encountering a wide variety of pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Furthermore, a multitude of microbes colonize mucosal surfaces, particularly the human intestine, which is estimated to harbor approximately 100 trillion bacteria. A unique immune system, termed “the mucosal immune system”, has evolved in vertebrates to enable the host to discriminate between the commensal microbiota and potential pathogenic microorganisms. For example, the mucosal immune system in the intestine must induce specific immunity towards pathogenic agents to enable effective host defense responses (e.g. through production of antigen-specific secretory-IgA). At the same time, the mucosal immune system must also suppress immune responses, or display tolerance towards commensal microbes and food components.

In recent years, several key studies have uncovered the cellular and molecular basis of the immune surveillance mechanisms that enable the mucosal immune system to sample antigens in the gut lumen. For example, in gut-associated lymphoid tissues, such as the Peyer’s patches in the small intestine, the uptake of antigens by epithelial M cells is important for the induction of antigen-specific IgA responses to those antigens. On the other hand, under certain circumstances, CX3CR1-expressing macrophages within the gut lamina propria are able to extend cytoplasmic processes between intestinal epithelial cells to directly sample luminal antigens. Mucus-secreting goblet cells can also provide passages (termed goblet cell-associated passages) which can promote the uptake of small soluble antigens from the gut lumen to the lamina propria, to help maintain oral tolerance. In recent years, a relatively rare population of intestinal epithelial cells, known as tuft cells, has been shown to sense helminth antigens and to produce the alarmin, IL-25, to trigger type 2 immune responses.

This Research Topic aims to provide a comprehensive overview of our current understanding of the cellular and molecular mechanisms, and the immunological significance of, mucosal antigen sampling. This Research Topic also aims to discuss the implications of these processes in the pathogenesis of mucosally-acquired infections, allergy and autoimmune diseases. We therefore welcome the submission of Original Research, Review and Mini-Review articles that cover, but are not limited to, the following topics:

1. Role of the innate mucosal immune system in the induction of antigen-specific mucosal immunity.
2. Mechanisms of antigen sampling at mucosal surfaces and their influence on mucosal immunity.
3. Maintenance of gut immune homeostasis.
4. How antigen sampling at mucosal surfaces influences tolerance induction in the gut.
5. Invasion mechanisms of pathogenic agents across mucosal surfaces.
6. Interactions between the microbiota and mucosal surfaces.
7. Sensing of helminth antigens at mucosal surfaces.

Image kindly provided by Dr. Shunsuku Kimura

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Keywords: Gut immunity, Oral tolerance, M cells, CX3CR1+ macrophages, GAPs, Tuft cells, Mucosal Immunity, Gut epithelial cells

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