Immunomodulation by Bifidobacterium infantis 35624 in the Murine Lamina Propria Requires Retinoic Acid-Dependent and Independent Mechanisms

Konieczna, Patrycja; Ferstl, Ruth; Ziegler, Mario; Frei, Remo; Nehrbass, Dirk; Lauener, Roger; Akdiş, Cezmi A.; O’Mahony, Liam

doi:10.1371/journal.pone.0062617

Cited by 80 publications

(63 citation statements)

References 33 publications

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“…DCs from the lamina propria of the small intestine can promote CD4 + T cell conversion to Tregs in a manner dependent on TGF-β and RA ). This capability of DCs is influenced by the microbiota, as feeding of mice with Bifidobacterium infantis results in elevated number of DCs capable of synthesizing RA as well as FoxP3 + cells in the lamina propria (Konieczna et al 2013).…”

Section: Retinoic Acid (Ra)mentioning

confidence: 99%

Metabolites: messengers between the microbiota and the immune system

2016

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The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases.The mammalian intestine harbors a dense and complex microbial community, termed the microbiota. The commensal microbiome and, in particular, the dense and diverse microbial community inhabiting the gastrointestinal tract play a pivotal role in the maintenance of organismal homeostasis and stable physiology. Research over the last decade has highlighted the concept that the eukaryotic host and its microbiota, rather than existing in isolation, compose a complex meta-organism termed the "holobiont," jointly regulating multiple aspects of mammalian physiology, including immune system development, metabolism, and nervous system function (Sommer and Backhed 2013). The interaction between the microbiota and the host is most prominent at mucosal surfaces, which provide an interface between the mostly microbe-free host, the microbiota, and the environment. At the same time, the presence of the microbial community within the eukaryotic host necessitates the development of a sophisticated immune system that controls and maintains a beneficial symbiosis of the holobiont through the continuous communication between the microbiome and the host.

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Section: Retinoic Acid (Ra)mentioning

confidence: 99%

Metabolites: messengers between the microbiota and the immune system

2016

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“…Administration of this bacterium to humans increases Foxp3 ϩ lymphocytes in peripheral blood, enhances interleukin-10 (IL-10) secretion ex vivo, and reduces the levels of circulating proinflammatory biomarkers in a wide range of patient groups (13,14). A number of host mechanisms that contribute to the anti-inflammatory activity of this microbe have been described, including Toll-like receptor 2 (TLR-2) and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) recognition and retinoic acid release by dendritic cells (13,(15)(16)(17). However, the bacterial-strain-specific structural and/or metabolic factors that contribute to these protective immune responses have as yet remained elusive.…”

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confidence: 99%

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T _H 17 Responses

Schiavi

Gleinser

Molloy

et al. 2016

Appl Environ Microbiol

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134

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The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immuneregulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPS neg ) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPS neg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPS neg did not protect against the development of colitis, with associated enhanced recruitment of IL-17 ؉ lymphocytes to the gut. Moreover, intranasal administration of sEPS neg also resulted in enhanced recruitment of IL-17 ؉ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local T H 17 responses. IMPORTANCEParticular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensalhost interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro. In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surfaceassociated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses. T he gut microbiota contributes significantly to host health via multiple mechanisms, including the digestion of foods, competitive exclusion of pathogens, enhancement of epithelial cell differentiation, and promotion of mucosa-associated lymphoid tissue proliferation (1, 2). Furthermore, accumulating evidence suggests that the composition and metabolic activity of the gut microbiota has profound effects on proinflammatory activity and the induction of immune tolerance within mucosal tissue (3-5). Certain microbes induce regulatory responses, while others induce effector responses, resulting in the case of healthy individuals in a balanced homeostatic...

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“…Moreover, this effect was abolished in CD103 + DCs from Il10 −/− , Tlr2 −/− , and Myd88 −/− mice. Konieczna et al [55] determined that B. longum subsp. infantis 35 624 increased numbers of CD103 + retinaldehyde dehydrogenase (RALDH) + DCs within the LP of mice and that this was associated with decreased Th1 and Th17 cells within the LP, and improved colitis outcomes.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

O’Neill

Schofield

Hall

2017

Emerging Topics in Life Sciences

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The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.

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Immunomodulation by Bifidobacterium infantis 35624 in the Murine Lamina Propria Requires Retinoic Acid-Dependent and Independent Mechanisms

Cited by 80 publications

References 33 publications

Metabolites: messengers between the microbiota and the immune system

Metabolites: messengers between the microbiota and the immune system

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T _H 17 Responses

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

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Immunomodulation by Bifidobacterium infantis 35624 in the Murine Lamina Propria Requires Retinoic Acid-Dependent and Independent Mechanisms

Cited by 80 publications

References 33 publications

Metabolites: messengers between the microbiota and the immune system

Metabolites: messengers between the microbiota and the immune system

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T H 17 Responses

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

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The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local T _H 17 Responses