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Introduction

This constant interplay between microorganisms, the gut, and associated lymphoid tissue is believed to result in a persistent stimulation, sensitation, and priming of the hosts immune system [6]. We have shown that specific strains of Lactobacillus are able to trigger increased translocation of STAT1 and NF-kB p65 in untransformed intestinal epithelial cells and that this signal translates further into macrophages.

NF-kB is a nuclear factor composed of several protein subunits regulating DNA transcription that is present in its inactive form in the cytoplasm, bound to the inhibitor molecule, IkB, while under non-stimulatory conditions. While translocation of p65 may result in various scenarios, translocation of STAT1 is triggered by interferon family proteins that further act as signaling molecules for an anti-microbial response [7] , [22]. Recent data have shown that TLR-9 signaling mediates the anti-inflammatory effects of probiotics.

Systemic administration of TLR-9 ligands reduces the severity of colonic injury and inflammation in models of experimental colitis [23] , in part through the TLR9-induced production of type I IFNs. De Kivit et al. Considerable differences could be observed while comparing translocations in IEC and macrophages.

The strain PCS 26, in contrast, did not increase the translocation rate of p65 in IEC but influenced a significantly higher rate in underlying macrophages; however, it did not statistically alter translocation of STAT1 in either cell type. LGG showed the highest overall influence on p65 translocation. This finding aligns with previous reports by Sanz et al. Moreover Lactobacillus plantarum and LGG have been shown to induce inflammatory cytokines also in dendritic cells, driving Th1 T cell proliferation in response to Salmonella, with L.

Several clinical studies that have shown specific lactic acid strains to promote sensitation and Th1-type immunity support our in vitro findings [5] , [27] however future studies should be conducted to show whether this effect can be considered systemic. Our data and prior observations, that several other Lactobacillus strains have been shown to induce anti-inflammatory responses [28] , demonstrate that the observed effects are very strain specific [5] , [18].

This difference has important implications for, among other things, probiotic supplementation as not every strain is suitable for every consumer or suitable at all, as in the case of immunocompromised newborns. We have further shown that the baseline level of STAT1 translocation in non-transformed IEC cultured alone or in the presence of macrophages differs drastically, whereas macrophages alone did not seem to be as dependent on co-cultivation. Haller et al. This underpins the importance of co-culture or 3D models for studies of host-microbe interactions and puts in question earlier immunomodulatory studies done in IEC monolayer set-ups, a concern raised previously [16] , [18].

Variances in model and cell line selection may partially explain apparently contradictory data found in literature on the pro- or anti-inflammatory actions of most common industrial strains such as Lactobacillus rhamnosus GG. We conclude that members of Lactobacillus spp. Future clinical studies should aim to elucidate whether probiotic interventions in infants might contribute to more balanced p65 and STAT signaling development in the immature gut as well as the gut-associated immune system.

National Center for Biotechnology Information , U. PLoS One. Published online Jan Markus M. Heimesaat, Editor. Author information Article notes Copyright and License information Disclaimer. Competing Interests: The authors have declared that no competing interests exist.

Introduction

Received Oct 31; Accepted Dec This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. This article has been cited by other articles in PMC. Abstract The early establishment of a complete microbiome has been shown to play an integral part in the development and maintenance of an intact intestine and its immune system, although much remains unknown about the specific mechanisms of immune modulation in newborns.

Introduction An established microbiome is prerequisite to the early development of the intestine in newborns acquiring tolerance and immunity [1]. Open in a separate window. Figure 1.


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Graphic outline of the study. Statistics Each experiment was performed in triplicate and results are expressed as mean percentages of each analyzed subset of cells in which nuclear translocation has occurred. Results Lactobacillus spp. Figure 2. Analysis of cell populations with imaging flow cytometry. Figure 3.

New Insights on Antiviral Probiotics: From Research to Applications (ebook)

Figure 4. Figure 5. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Abstract Aims: To determine if live recombinant Lactococcus lactis strains expressing rotavirus VP7 antigen are immunogenic in mice. Rotavirus infection and cellular extract Fetal rhesus monkey kidney cell line MA was grown in confluent monolayers and infected with Simian rotavirus SA11 strain at a multiplicity of infection MOI of c. Virus neutralization assay Neutralization activity of sera from immunized animals was performed using the SA11 rotavirus strain by the infection of MA cells at a MOI of Oral immunization of mice Animals used in the experiments were kept handled according to the Italian rules for ethical handling of animals.

Results Secretion of VP7 in L. Figure 1 Open in figure viewer PowerPoint. Cell wall anchoring of rVP7 in L. Immunogenicity of rVP7 produced in L. Figure 2 Open in figure viewer PowerPoint.


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Antibody response in orally immunized mice In order to study if oral inoculation of L. Figure 3 Open in figure viewer PowerPoint. Rotavirus neutralization capacity of serum antibodies To further study the neutralization activity of the antibodies elicited in mice following oral immunization with L. Figure 4 Open in figure viewer PowerPoint. Discussion Here we show that it is possible to express the rotavirus VP7 antigen in the food grade bacterium Lactococcus lactis and that this recombinant protein maintains antigenic properties.

Acknowledgements We thank G.

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Imad Al Kassaa (Author of New Insights on Antiviral Probiotics)

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