Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium

Dickinson, Eva C.; Gorga, Joan C.; Garrett, Melissa; Tuncer, Recep; Boyle, Patricia; Watkins, Simon C.; Alber, Sean; Parizhskaya, Maria; Trucco, Massimo; Rowe, Marc I.; Ford, Henri R.

doi:10.1016/s0039-6060(98)70132-1

Cited by 75 publications

(21 citation statements)

References 20 publications

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“…IgA prevented epithelial cell apoptosis that occurred with combined exposure to hypoxia and E. coli [25]. This is consistent with an in vivo description of the protective effect of orally supplemented IgA, but not IgG, on villous architecture and bacterial translocation in a neonatal rabbit model of milk formula induced injury [26]. The role of the HIF pathway in regulating IgA synthesis and transcytosis in the intestine remains to be determined.…”

Section: Intra-luminal Barrier and Hypoxiasupporting

confidence: 77%

Targeting Hypoxia to Augment Mucosal Barrier Function

Kelly

Colgan

2012

JEBP

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Sites of inflammation are associated with profound changes in tissue metabolism. Studies in vitro and in vivo have shown that the activation of the hypoxia-inducible factor (HIF) serves as an adaptive pathway for the resolution of inflammation associated with various murine disease models. The resolution of disease occurs, at least in part, through transcriptional regulation of non-classical epithelial barrier genes. There is significant recent interest in harnessing hypoxia-inducible pathways, including targeting the HIF and the proyl-hydroxylase (PHD) enzymes that stabilize HIF, to promote mucosal healing. Here, we review the signaling pathways involved and define how hypoxia-associated signaling provides mechanistic insight into augmenting barrier function in mucosal inflammatory disease.

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Section: Intra-luminal Barrier and Hypoxiasupporting

confidence: 77%

Targeting Hypoxia to Augment Mucosal Barrier Function

Kelly

Colgan

2012

JEBP

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“…The role of secretory IgA at mucosal surfaces and its role in the protection against B. anthracis has already been established [10]. Antigen-specific secretory IgA can exert its beneficial effects by interfering with the early events of infection through the inhibition of bacterial attachment and colonization, or by facilitating phagocytosis and subsequent antigen presentation by DCs and macrophages [30]. L. gasseri expressing PA-DCpep induced a significant amount of IgA compared to PBS-treated mice ( Fig.…”

Section: Discussionmentioning

confidence: 90%

Colonic Immune Stimulation by Targeted Oral Vaccine

et al. 2013

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BackgroundCurrently, sufficient data exist to support the use of lactobacilli as candidates for the development of new oral targeted vaccines. To this end, we have previously shown that Lactobacillus gasseri expressing the protective antigen (PA) component of anthrax toxin genetically fused to a dendritic cell (DC)-binding peptide (DCpep) induced efficacious humoral and T cell-mediated immune responses against Bacillus anthracis Sterne challenge.Methodology/Principal FindingIn the present study, we investigated the effects of a dose dependent treatment of mice with L. gasseri expressing the PA-DCpep fusion protein on intestinal and systemic immune responses and confirmed its safety. Treatment of mice with different doses of L. gasseri expressing PA-DCpep stimulated colonic immune responses, resulting in the activation of innate immune cells, including dendritic cells, which induced robust Th1, Th17, CD4+Foxp3+ and CD8+Foxp3+ T cell immune responses. Notably, high doses of L. gasseri expressing PA-DCpep (1012 CFU) were not toxic to the mice. Treatment of mice with L. gasseri expressing PA-DCpep triggered phenotypic maturation and the release of proinflammatory cytokines by dendritic cells and macrophages. Moreover, treatment of mice with L. gasseri expressing PA-DCpep enhanced antibody immune responses, including IgA, IgG1, IgG2b, IgG2c and IgG3. L. gasseri expressing PA-DCpep also increased the gene expression of numerous pattern recognition receptors, including Toll-like receptors, C-type lectin receptors and NOD-like receptors.Conclusion/SignificanceThese findings suggest that L. gasseri expressing PA-DCpep has substantial immunopotentiating properties, as it can induce humoral and T cell-mediated immune responses upon oral administration and may be used as a safe oral vaccine against anthrax challenge.

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“…Secretory IgA of the milk is known to inhibit the association of bacteria with the gut mucosa and reduce bacterial penetration in the gut. In neonates, IgA supplementation is known to avoid bacterial translocation by enhancing gut mucosal barrier function and therefore neonatal gut-origin sepsis [180, 181]. As pointed before, lactoferrin, which is present in human milk, is a component of innate immunity and has antimicrobial activity.…”

Section: Neonatal Innate Immune Response Infections and Sepsismentioning

confidence: 99%

Neonatal Immune Adaptation of the Gut and Its Role during Infections

Tourneur

Chassin

2013

Clinical and Developmental Immunology

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The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.

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Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium

Cited by 75 publications

References 20 publications

Targeting Hypoxia to Augment Mucosal Barrier Function

Targeting Hypoxia to Augment Mucosal Barrier Function

Colonic Immune Stimulation by Targeted Oral Vaccine

Neonatal Immune Adaptation of the Gut and Its Role during Infections

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