title: Homeostatic impact of indigenous microbiota and secretory immunity.
abstract: In the process of evolution, the mucosal immune system has generated two layers of anti-inflammatory defence: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonisation of microorganisms and dampen penetration of potentially dangerous antigens; and (2) suppressive mechanisms to avoid local and peripheral hypersensitivity to innocuous antigens, particularly food proteins and components of commensal bacteria. When induced via the gut, the latter phenomenon is called 'oral tolerance', which mainly depends on the development of regulatory T (Treg) cells in mesenteric lymph nodes to which mucosal dendritic cells (DCs) carry exogenous antigens and become conditioned for induction of Treg cells. Mucosally induced tolerance appears to be a rather robust adaptive immune function in view of the fact that large amounts of food proteins pass through the gut, while overt and persistent food allergy is not so common. DCs are 'decision makers' in the immune system when they perform their antigen-presenting function, thus linking innate and adaptive immunity by sensing the exogenous mucosal impact (e.g. conserved microbial molecular patterns). A balanced indigenous microbiota is required to drive the normal development of both mucosa-associated lymphoid tissue, the epithelial barrier with its secretory IgA (and IgM) system, and mucosally induced tolerance mechanisms including the generation of Treg cells. Notably, polymeric Ig receptor (pIgR/SC) knock-out mice that lack secretory IgA and IgM antibodies show reduced epithelial barrier function and increased uptake of antigens from food and commensal bacteria. They therefore have a hyper-reactive immune system and show predisposition for systemic anaphylaxis after sensitisation; but this development is counteracted by enhanced oral tolerance induction as a homeostatic back-up mechanism.
authors.affiliation: Department and Institute of Pathology, Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation (CIR), Oslo University Hospital, Rikshospitalet, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Brandtzaeg
mesh_terms: D000818:Animals; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D054892:Metagenome; D051379:Mice
chemical_list: D007071:Immunoglobulin A, Secretory; D007075:Immunoglobulin M; C033027:secretory IgM