Article

An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System

Harvard University, Cambridge, Massachusetts, United States
Cell (Impact Factor: 32.24). 08/2005; 122(1):107-18. DOI: 10.1016/j.cell.2005.05.007
Source: PubMed

ABSTRACT

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.

Full-text preview

Available from: wisc.edu
  • Source
    • "Presently, it is apparent that the microbiota and its products have a profound effect on the development and maintenance of the immune system. Germ-free animals, for example, have an impaired immune system that can be functionally restored after the inoculation of commensal bacteria (MacPherson et al., 2001MacPherson et al., , 2002 Mazmanian et al., 2005). The extent of dependency of the immune system on commensals may even suggest the commensalocentric view. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thegutecosystemwithmyriadsofmicroorganismsandthehighconcentrationofimmunesystemcellscanbeconsideredasaseparateorganonitsown.Thebalancedinteractionbetweenthehostandmicrobialcellshasbeenshapedduringthelongco-evolutionaryprocess.Indysbioticconditions,however,thisbalanceiscompromisedandresultsinabnormalinteractionbetweenthehostandmicrobiota.Itishypothesizeherethatthechangedspectrumofmicrobialenzymesinvolvedinpost-translationalmodificationofproteins(PTMP)maycontributetotheaberrantmodificationofhostproteinsthusgeneratingautoimmuneresponsesbythehost,resultinginautoimmunediseases.
    Full-text · Article · Mar 2016 · Frontiers in Microbiology
    • "The genome loci for EPS biosynthesis appear to be hotspots for genetic recombination in many Lactobacilli and are therefore highly structurally variable with different sugar monomers and also different modes of linkage, substitution, and branching (Francius et al., 2008), even among strains of the same species. EPS from probiotics have been shown to induce or inhibit cytokine production in immune cells in vitro (Yasuda et al., 2008), attenuate ileitis (Mazmanian et al., 2005), and suppress tumor growth in mouse models. Some proteins of lactobacilli appear to be glycosylated (Francius et al., 2008) and may interact with CLR that are involved in the recognition and capture of antigens by antigen-presenting cells such as dendritic cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gnotobiology technology for the breeding of experimental mice originated in the first half of the twentieth century. Earlier studies conducted in germ-free animals revealed the importance of the microbiota in the development of the immune system, gut morphology, and metabolism. These seminal studies have been confirmed and complemented by recent work that exploits the use of modern gnotobiotic technology as well as the combination of high-throughput molecular techniques to study the composition and metabolic capacity of the intestinal microbiota. From a historical perspective, this chapter discusses the evolution of theory concerning complex host-microbiota interactions and probiotics species. It also reviews the current evidence for a role of maladaptive interactions in the development of disease within and beyond the gastrointestinal tract.
    No preview · Article · Dec 2015
  • Source
    • "Germ-free mice have immature isolated lymphoid follicles, small Peyer's patches that lack germinal centres, and an absence of distinct T and B cell follicles in mesenteric lymph nodes and spleen, which mature following colonization (Adachi et al., 1997; Bouskra et al., 2008). Moreover, the Bacteroides fragilis product polysaccharide A (PSA) can stimulate expansion of spleen lymphocyte follicles (Mazmanian et al., 2005). Microbial stimulation is required to induce site-specific expansion and maturation of innate immune cells, and directly relates to the level of microbiota complexity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently this community of bacteria and perturbation of its colonization in early life has been linked to a number of diseases. Many factors are capable of influencing this colonization and ultimately leading to an altered gut microbiota which is known to affect key systems within the body. The impact of the microbial composition of our gastrointestinal tract on systems outside the gut is also becoming apparent. Here we highlight the factors that are capable of impacting on microbiota colonization in early-life and the developing systems that are affected and finally how this may be involved in the manifestation of childhood diseases. Birth Defects Research (Part C), 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Dec 2015 · Birth Defects Research Part C Embryo Today Reviews
Show more