Protective effects of <i>Lactobacillus reuteri</i> and <i>Bifidobacterium infantis</i> in murine models for colitis do not involve the vagus nerve

Kleij, Hanneke Paulina van der; O’Mahony, Cáitlín; Shanahan, Fergus; O’Mahony, Liam; Bienenstock, John

doi:10.1152/ajpregu.90434.2008

Cited by 63 publications

(44 citation statements)

References 36 publications

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“…In the GI tract, expansion of antigen-specific Tregs is tightly regulated . This observation is in line with a previous report by van der Kleij H et al, showing that VGX had no effect in chronic model of colitis (28). Interestingly, these data are in contrast with the worsening effect of VGX in DSS colitis models.…”

Section: Discussionsupporting

confidence: 93%

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

Giovangiulio

Bosmans

Meroni

et al. 2016

Mol Med

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Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR -/-mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR -/-mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. online address: http://www.molmed.org

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Section: Discussionsupporting

confidence: 93%

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

Giovangiulio

Bosmans

Meroni

et al. 2016

Mol Med

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“…Mice were administered B. longum 35624, sEPS neg , or sEPS comp daily by oral gavage. As previously described, B. longum 35624 treatment prevented weight loss and disease symptoms in this model (34). However, mice treated with the sEPS neg strain exhibited significant weight loss and severe disease symptoms, while restoration of EPS production in the sEPS comp strain promoted a response similar to that of mice treated with B. longum 35624 (Fig.…”

Section: Generation Of An Isogenic Exopolysaccharide-negative Derivatsupporting

confidence: 78%

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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“…[15][16][17] In the present study, the LAB-E. coli shuttle vector pHIL253 was constructed for expression and secretion of CTB. The pHIL253 vector contains ori-177 from pHY300PLK and pAMβ1 from pIL253, along with the ampicillin resistance gene of pHY300PLK and the erythromycin resistance gene of pIL253 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Expression and Secretion of Cholera Toxin B Subunit in Lactobacilli

Okuno

Kashige

Satho

et al. 2013

Biological & Pharmaceutical Bulletin

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Lactic acid bacteria (LAB) are used in various fields, including in food and medical supplies. There has been a great deal of research into vaccine development using LAB as carriers due to their "generally recognized as safe" status. Cholera is an infectious disease that causes diarrhea due to cholera toxin (CT) produced by Vibrio cholerae. The pentameric cholera toxin B (CTB) subunit has no toxicity, and is used as an antigen in cholera vaccines and as a delivery molecule in vaccines to various diseases. In this study, we generated recombinant LAB expressing and secreting CTB. Here, we first report that CTB expressed and secreted from LAB bound to GM1 ganglioside. The secreted CTB was purified, and its immunogenicity was determined by intranasal administration into mice. The results of the present study suggested that it may be useful as the basis of a new oral cholera vaccine combining LAB and CTB.

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Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

Cited by 63 publications

References 36 publications

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

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

Expression and Secretion of Cholera Toxin B Subunit in Lactobacilli

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Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

Cited by 63 publications

References 36 publications

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

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

Expression and Secretion of Cholera Toxin B Subunit in Lactobacilli

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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