An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

By S. Mazmanian, C. Liu, A. Tzianabos, D. Kasper. Cell, 2005

2,832 citations recorded by the source corpus.

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.

Subfields: Food Science, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b2d2d82603f8e36ded5b7b7cd24effbcb12e5bfe

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Citations in the corpus

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases (2017, background): “Mazmanian et al [103] showed that during colonization of B.”
The role of microbiome in central nervous system disorders (2013, positive): “fragilis capsular polysaccharide A (PSA) was sufficient to expand splenic total CD4 T cells and intestinal Foxp3CD4 Tregs, which suggested that specific commensal antigens could drive immune regulation (Mazmanian et al., 2005; Round and Mazmanian, 2010).”
IgA response to symbiotic bacteria as a mediator of gut homeostasis. (2007, result): “5-fold (Figure S2), consistent with a CD4 T-helper 1 (Th1) environment (Mazmanian et al., 2005).”
Carbohydrate metabolism in Bifidobacteria (2011, background): “Research on the gut microbiota composition in humans, as supported by work in gnotobiotic mouse models, has revealed the existence of a mutualistic relationship between humans and the gut microbiota, which acts as a virtual organ to (1) influence maturation of the immune system [76, 90], (2) defend ”
The immune system and the gut microbiota: friends or foes? (2010, background): “and decreased numbers of memory CD4 + T cells, and cytokine production by these T cells shows a T H 2-type profil”
Plasticity of CD4+ T cell lineage differentiation. (2009, background): “For example, the symbiont Bacteroides fragilis, via production of polysaccharide A (PSA), influences immune homeostasis and protects animals from experimental colitis by inhibiting Th17 cell differentiation and inducing IL-10 production (Mazmanian et al., 2005; Mazmanian et al., 2008).”
Role of the Microbiota in Immunity and inflammation (2014, background): “…in the gastrointestinal tract, where germ-freemice are characterized by smaller Peyer’s patch size and a reduced number of CD4+T cells and IgA-producing plasma cells (Bauer et al., 1963; Hamada et al., 2002; Macpherson et al., 2001; Mazmanian et al., 2005; Smith et al., 2007; Talham et al., 1999).”
Mining the human gut microbiota for immunomodulatory organisms (2017, positive): “The gut microbiota plays an important role in educating and modulating the host immune system (Mazmanian et al., 2005; Schirmer et al., 2016).”
Specific microbiota direct the differentiation of Th17 cells in the mucosa of the small intestine (2008, positive): “For example, it has been reported that the gut commensal, Bacteroides fragilis, affects systemic Th1 responses through the action of the bacterial-derived polysaccharide A (PSA) (Mazmanian et al., 2005).”
Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. (2014, background): “Cell-associated saccharides such as lipopolysaccharides (Park et al., 2009), capsular polysaccharides (Kadioglu et al., 2008), and polysaccharide A (Mazmanian et al., 2005; Mazmanian et al., 2008) are known to play key roles in microbe-host and microbe-microbe interactions, while diffusible…”
Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection (2012, background): “Cell Host tered orally to animals is associated with CD11c DCs in the MLN (Mazmanian et al., 2005).”
Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens (2010, background): “gov/sites/entrez?Db=genomeprj&cmd=ShowDetailView&TermToSearch=13111"> Bacteroides fragilis , termed polysaccharide A, is known to have a key role in the development of the immune system in germ-free mic”
Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “Reconstitution of mice with Bacteroides fragilis, an abundant commensal, reverts these defects via immunogenic presentation of the zwitterionic polysaccharide A (PSA) and priming of splenic Th1 cells [28].”