| 1. |
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| 2. |
- Gebremariam, Hanna G., et al.
(författare)
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Lactobacillus gasseri Suppresses the Production of Proinflammatory Cytokines in Helicobacter pylori-Infected Macrophages by Inhibiting the Expression of ADAM17
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The ability of Helicobacter pylori to evade the host immune system allows the bacterium to colonize the host for a lifetime. Long-term infection with H. pylori causes chronic inflammation, which is the major risk factor for the development of gastric ulcers and gastric cancer. Lactobacilli are part of the human microbiota and have been studied as an adjunct treatment in H. pylori eradication therapy. However, the molecular mechanisms by which lactobacilli act against H. pylori infection have not been fully characterized. In this study, we investigated the anti-inflammatory effects of Lactobacillus strains upon coincubation of host macrophages with H. pylori. We found that Lactobacillus gasseri Kx110A1 (L. gas), a strain isolated from a human stomach, but not other tested Lactobacillus species, blocked the production of the proinflammatory cytokines TNF and IL-6 in H. pylori-infected macrophages. Interestingly, L. gas also inhibited the release of these cytokines in LPS or LTA stimulated macrophages, demonstrating a general anti-inflammatory property. The inhibition of these cytokines did not occur through the polarization of macrophages from the M1 (proinflammatory) to M2 (anti-inflammatory) phenotype or through the altered viability of H. pylori or host cells. Instead, we show that L. gas suppressed the release of TNF and IL-6 by reducing the expression of ADAM17 (also known as TNF-alpha-converting enzyme, TACE) on host cells. Our findings reveal a novel mechanism by which L. gas prevents the production of the proinflammatory cytokines TNF and IL-6 in host macrophages.
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| 3. |
- Govindaraj, Dhanapal, et al.
(författare)
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Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy
- 2024
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Ingår i: Clinical & Translational Immunology (CTI). - : WILEY. - 2050-0068. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Extremely preterm (EPT; gestational week < 28 + 0, < 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants. Methods: Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of Lactobacillus reuteri DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads. Results: The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-gamma, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses. Conclusions: Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.
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| 4. |
- Haileselassie, Yeneneh, et al.
(författare)
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Lactobacillus reuteri and Staphylococcus aureus differentially influence the generation of monocyte-derived dendritic cells and subsequent autologous T cell responses
- 2016
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Ingår i: Immunity, Inflammation and Disease. - : Wiley. - 2050-4527. ; 4:3, s. 315-326
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In early-life, the immature mucosal barrier allows contact between the gut microbiota and the developing immune system. Due to their strategic location and their ability to sample luminal antigen, dendritic cells (DC) play a central role in the interaction of microbes and immune cells in the gut. Here, we investigated how two bacteria associated with opposite immune profiles in children, that is, Lactobacillus (L.) reuteri and Staphylococcus (S.) aureus, influenced the differentiation of monocytes in vitro as well how the generated DC impacted T cell responses.Methods: We exposed monocyte cultures to cell-free supernatants (CFS) from these bacteria during their differentiation to DC.Results: The presence of L. reuteri-CFS during DC differentiation resulted in DC with a more mature phenotype, in terms of up-regulated surface markers (HLA-DR, CD86, CD83, CCR7) and enhanced cytokine production (IL6, IL10, and IL23), but had a reduced phagocytic capacity compared with non-treated monocyte-derived DC (Mo-DC). However, upon LPS activation, L. reuteri-CFS-generated DC displayed a more regulated phenotype than control Mo-DC with notable reduction of cytokine responses both at mRNA and protein levels. In contrast, S. aureus-CFS-generated DC were more similar to control Mo-DC both without and after LPS stimulation, but they were still able to induce responses in autologous T cells, in the absence of further T cell stimulation.Conclusions: We show that bacterial signals during DC differentiation have a profound impact on DC function and possibly also for shaping the T cell pool.
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| 5. |
- Haileselassie, Yeneneh, 1983-, et al.
(författare)
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Postbiotic Modulation of retinoic acid imprinted Mucosal-like Dendritic cells by Probiotic Lactobacillus reuteri 17938 In Vitro
- 2016
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 7, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CFS) influenced retinoic acid (RA)-driven mucosal-like dendritic cells (DC) and their subsequent effect on T regulatory cells (Treg) in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression, and a downregulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB, and TNF). Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by downregulating most genes involved in antigen uptake, antigen presentation, and signal transduction as well as several chemokine receptors, while upregulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In cocultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.
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| 6. |
- Johansson, Maria A., et al.
(författare)
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Probiotic Lactobacilli Modulate Staphylococcus aureus-Induced Activation of Conventional and Unconventional T cells and NK Cells
- 2016
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacilli are probiotic commensal bacteria and potent modulators of immunity. When present in the gut or supplemented as probiotics, they beneficially modulate ex vivo immune responsiveness. Further, factors derived from several lactobacilli strains act immune regulatory in vitro. In contrast, Staphylococcus aureus (S. aureus) is known to induce excessive T cell activation. In this study, we aimed to investigate S. aureus-induced activation of human mucosal-associated invariant T cells (MAIT cells), gamma delta T cells, NK cells, as well as of conventional CD4(+) and CD8(+) T cells in vitro. Further, we investigated if lactobacilli-derived factors could modulate their activation. PBMC were cultured with S. aureus 161: 2 cell-free supernatants (CFS), staphylococcal enterotoxin A or CD3/CD28-beads alone, or in combination with Lactobacillus rhamnosus GG-CFS or Lactobacillus reuteri DSM 17938-CFS and activation of T and NK cells was evaluated. S. aureus-CFS induced IFN-gamma and CD107a expression as well as proliferation. Costimulation with lactobacilli-CFS dampened lymphocyte-activation in all cell types analyzed. Preincubation with lactobacilli-CFS was enough to reduce subsequent activation, and the absence of APC or APC-derived IL-10 did not prevent lactobacilli-mediated dampening. Finally, lactate selectively dampened activation of unconventional T cells and NK cells. In summary, we show that molecules present in the lactobacilli-CFS are able to directly dampen in vitro activation of conventional and unconventional T cells and of NK cells. This study provides novel insights on the immune-modulatory nature of probiotic lactobacilli and suggests a role for lactobacilli in the modulation of induced T and NK cell activation.
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| 7. |
- Kupferschmidt, Natalia, et al.
(författare)
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Mesoporous silica particles potentiate antigen-specific T-cell responses
- 2014
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Ingår i: Nanomedicine. - 1743-5889 .- 1748-6963. ; 9:12, s. 1835-1846
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the adjuvant effect of mesoporous silica particles and their capability of modifying an already existing allergic Th2-like immune response. Materials & methods: The adjuvant effect of Santa Barbara Amorphous-15 (SBA-15) mesoporous silica particles was studied in an antigen-specific ovalbumin (OVA) system in vitro and in vivo. The capacity of the OVA-loaded SBA-15 particles (SBA-15-OVA) to modify an existing immune response was assessed in a murine allergy model. Results: SBA-15-OVA induced significantly stronger OVA-specific splenocyte proliferation compared with OVA alone. Significantly higher IFN-gamma production was observed in ex vivo OVA-stimulated splenocytes from SBA-15-OVA-immunized mice compared with mice injected with only SBA-15 or OVA. Treatment of OVA-sensitized mice with SBA-15-OVA modified the immune response with significantly lower serum levels of OVA-specific IgE and higher IgG levels compared with the alum-OVA-treated group. Conclusion: The results are promising for the continued development of mesoporous silica materials for therapeutic applications.
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| 8. |
- Kupferschmidt, Natalia, et al.
(författare)
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Mesoporous silica particles potentiate antigen specific T cell responses
- 2014
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Ingår i: Nanomedicine. - : Future Medicine Ltd. - 1743-5889 .- 1748-6963. ; 9:12, s. 1835-1846
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the adjuvant effect of mesoporous silica particles and their capability of modifying an already existing allergic Th2-like immune response. Materials & methods: The adjuvant effect of Santa Barbara Amorphous-15 (SBA-15) mesoporous silica particles was studied in an antigen-specific ovalbumin (OVA) system in vitro and in vivo. The capacity of the OVA-loaded SBA-15 particles (SBA-15-OVA) to modify an existing immune response was assessed in a murine allergy model. Results: SBA-15-OVA induced significantly stronger OVA-specific splenocyte proliferation compared with OVA alone. Significantly higher IFN-γ production was observed in ex vivo OVA-stimulated splenocytes from SBA-15-OVA-immunized mice compared with mice injected with only SBA-15 or OVA. Treatment of OVA-sensitized mice with SBA-15-OVA modified the immune response with significantly lower serum levels of OVA-specific IgE and higher IgG levels compared with the alum-OVA-treated group. Conclusion: The results are promising for the continued development of mesoporous silica materials for therapeutic applications. Original submitted 18 January 2013; Revised submitted 30 August 2013
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| 9. |
- Petursdottir, Dagbjort H., et al.
(författare)
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Early-Life Human Microbiota Associated With Childhood Allergy Promotes the T Helper 17 Axis in Mice
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota influences immune maturation during childhood, and is implicated in early-life allergy development. However, to directly study intestinal microbes and gut immune responses in infants is difficult. To investigate how different types of early-life gut microbiota affect immune development, we collected fecal samples from children with different allergic heredity (AH) and inoculated germ-free mice. Immune responses and microbiota composition were evaluated in the offspring of these mice. Microbial composition in the small intestine, the cecum and the colon were determined by 16S rRNA sequencing. The intestinal microbiota differed markedly between the groups of mice, but only exposure to microbiota associated with AH and known future allergy in children resulted in a T helper 17 (Th17)-signature, both systemically and in the gut mucosa in the mouse offspring. These Th17 responses could be signs of a particular microbiota and a shift in immune development, ultimately resulting in an increased risk of allergy.
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| 10. |
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