Respiratory allergy control by probiotic fermented milk intake: a mouse model from weaning to maturity

2020 ◽  
Vol 11 (8) ◽  
pp. 767-778
Author(s):  
E.M.M. Velez ◽  
R. Weill ◽  
M.C. Maldonado-Galdeano ◽  
G. Perdigón

This study is based on our previous research showing that commercial probiotic fermented milk (PFM) intake mitigates respiratory allergy development to ovalbumin (OVA) in adult mice (6-weeks old) increasing specific immunoglobulin (Ig)G2a and interferon (IFN)-γ rather than IgE. The aim was to determine if PFM exerts a protective effect when an allergy model is induced 5 days after weaning and whether the mechanisms involved are similar to those previously reported. Before inducing allergy, a group of 21-day old BALB/c mice received PFM for 10 days to analyse the impact on intestinal epithelial cells (IECs) activation. Two more groups received PFM for 5 days and were sensitised with OVA; only one group continued taking PFM until the end of the experiment. Sensitisation scheme: 3 OVA injections 1% in phosphate buffered saline (PBS) plus 7 days OVA aerosol exposure and re-stimulus 15 days later. The contents of specific- IgE, IgG, total-secretory-IgA and Th1/Th2 balance in serum, bronchoalveolar lavage (BAL) and gut were measured at 7 and 15 days post-sensitisation (dPS) and 2 days post-re-stimulus (2dPR). Treg cells in lungs were also quantified. Results were compared with normal and sensitised controls. PFM induced mild activation of IECs increasing monocyte chemoattractant protein-1 (MCP-1 or CCL2) and interleukin (IL)-6 production. In sensitised mice, PFM controlled the response inducing IgG rather than IgE at 7 and 15-dPS and 2dPR (60 days old). Th1-balance (IFN-γ) was favoured by PFM in lungs at 7 dPS with low levels of IL-10 released to regulate the response. Total-S-IgA increased in lungs and gut; however, PFM intake did not affect Treg cells in lungs. PFM maintains controlled stimulation of the immune cells involved in Th1 response, favouring IgG at the respiratory mucosal site. Although the effect was not as strong as that reported previously, PFM promoted maturation and activation of gut immune cells preserving intestinal homeostasis and lung immune response.

2021 ◽  
Vol 12 (2) ◽  
pp. 175-186
Author(s):  
E. Velez ◽  
I. Novotny-Nuñez ◽  
S. Correa ◽  
G. Perdigón ◽  
C. Maldonado-Galdeano

Allergies are a world increasing health issue and most treatments are oriented to alleviate symptoms. Probiotics have several health benefits including the improvement of the immune system. In previous work we found that consumption of commercial probiotic fermented milk (PFM) significantly reduced specific-immunoglobulin (Ig) E in serum and lungs by increasing specific-IgG and controlled allergic response to ovalbumin (OVA) in an adult mouse respiratory allergy model. Here we continued our study determining the mechanism triggered in the gut by the PFM ingestion that influenced the results previously reported. Five groups of BALB/c mice were assessed: normal-control, basal (drinks PFM five days without OVA sensitisation), sensitisation-control (no PFM intake), previous and continuous-PFM administration. Allergen administration: 3 OVA injections (1% in PBS) followed by aerosols exposure for 7 days. We determined total secretory-IgA and cytokines in small intestine (SI) fluid; CD11b+, CD103+, IgA+ cells and cytokine producing cells in SI tissue. In lungs we analysed co-expression of CD4/interferon (IFN)-γ or CD4/interleukin (IL)-10, IgE+ cells and IL-12 production. Results: continuous intake of PFM increased the expression of CD103 marker and decreased CD11b and pro-inflammatory cytokines. Coexpression of CD4/IFN-γ was confirmed in lungs of animals that consumed PFM continuously. This group had a lower count of IgE+ cells and a higher concentration of IL-12. The consumption of PFM reinforces the mucosal barrier by increasing IgA+ cells and induces signalling from the intestine to the lungs by increasing the expression of CD103+ dendritic cells related to regulatory mechanisms. The results found in this work together with those previously reported demonstrated that the intake of PFM induces a clear balance towards the Th1 response, preventing the Th2 allergic response by controlling the previously reported IgE level. According to our model, the intake of PFM could be a good strategy to alleviate the development of allergies.


2015 ◽  
Vol 114 (4) ◽  
pp. 566-576 ◽  
Author(s):  
Eva M. M. Velez ◽  
Carolina Maldonado Galdeano ◽  
Esteban Carmuega ◽  
Ricardo Weill ◽  
María E. Bibas Bonet ◽  
...  

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisation process. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treating allergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed with PFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-γ (IFN-γ), IL-4, IL-10 and total secretory IgA (S-IgA) were measured in the supernatants of macerated lungs or in the BALF. The levels of IgA+, CD4+and CD8+T lymphocytes and F4/80+cells were measured in the lungs by immunofluorescence. Inducible CD4+/CD25/Foxp3+regulatory T (Treg) cells were evaluated in the lungs. PFM shifted the T helper (Th)2 profile response towards a Th1 response that led to the production of IgG instead of IgE, with increasing levels of IL-10 and IFN-γ that play an important role in immunomodulation exerted by PFM administration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels of anti-OVA-specific IgG and total S-IgA. PFM did not influence Tregcells in treated mice. Consumption of PFM could be a promising strategy in the amelioration of airway allergies, considering that the effect is mediated by the production of IgG through the activation of Th1 instead of the direct activation of Th2 cells to produce IgE.


2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 4-4
Author(s):  
Haider Mahdi ◽  
Ying Ni

4 Background: Ovarian and MSS endometrial cancers are characterized by immunosuppressive microenvironment (TME) and low response to immunotherapy with checkpoint inhibitors (CPI). Targeting immunosuppressive factors within TMErepresents an attractive approach to enhance response to CPI. Therefore, we sought to investigate different immunogenomic signatures and immune cells within TME and correlate them with survival. Methods: We used whole transcriptome sequencing of matched tumor-normal samples from 38 uterine serous cancer and TCGA data of ovarian (n = 374) and endometrial cancers (n = 541). Immunogenomic signatures focusing on Transforming Growth Factor (TGFβ), 18-genes IFN-γ and myeloid signatures (CD47 and B7H4 expressions) and immune cell abundance were investigated. Gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separate the survival in the pilot cohort. Then the score was tested in TCGA RNAseq datasets. Population abundance of tissue-infiltrating immune cells were estimated using MCPcounter R package from bulk transcriptome data. Results: Higher IFN-γ and lower TGF-β signatures predicted better survival for endometrial and ovarian cancers (p < 0.05). The impact of TGF-β was higher in MSI-H vs. MSS cancers (p = 0.013 vs. 0.09). High CD47 predicted poor survival in endometrial cancer. Combined IFN-γ and TGF-β signatures predicted survival in the ovarian and endometrial cohorts (p < 0.001). Combined IFN-γ and CD47 expression predicted survival in endometrial cancer (p = 0.033). Analysis of immune cell abundance revealed enrichment of monocytic lineage and neutrophils but paucity of cytotoxic T-cells, NK cells, dendritic cells and B-cells. Immune cell abundance is being correlated with survival. Conclusions: Our data support the role of immunogenomic markers in predicting survival. We are evaluating these markers in predicting response to CPI in a pilot cohort. Immunogenomic markers represent the tumor microenvironment, can potentially guide rationale combination immunotherapy.


2018 ◽  
Vol 115 (11) ◽  
pp. E2585-E2593 ◽  
Author(s):  
Marisella Panduro ◽  
Christophe Benoist ◽  
Diane Mathis

Skeletal muscle regeneration is a highly orchestrated process that depends on multiple immune-system cell types, notably macrophages (MFs) and Foxp3+CD4+ regulatory T (Treg) cells. This study addressed how Treg cells rein in MFs during regeneration of murine muscle after acute injury with cardiotoxin. We first delineated and characterized two subsets of MFs according to their expression of major histocompatibility complex class II (MHCII) molecules, i.e., their ability to present antigens. Then, we assessed the impact of Treg cells on these MF subsets by punctually depleting Foxp3+ cells during the regenerative process. Treg cells controlled both the accumulation and phenotype of the two types of MFs. Their absence after injury promoted IFN-γ production, primarily by NK and effector T cells, which ultimately resulted in MF dysregulation and increased inflammation and fibrosis, pointing to compromised muscle repair. Thus, we uncovered an IFN-γ–centered regulatory layer by which Treg cells keep MFs in check and dampen inflammation during regeneration of skeletal muscle.


2020 ◽  
Vol 11 ◽  
Author(s):  
Christopher W.M. Link ◽  
Christina N. Rau ◽  
Christopher C. Udoye ◽  
Mohab Ragab ◽  
Rabia Ü. Korkmaz ◽  
...  

Food allergies are common, costly and potentially life-threatening disorders. They are driven by Th2, but inhibited by Th1 reactions. There is also evidence indicating that IL-2 agonist treatment inhibits allergic sensitization through expansion of regulatory T cells. Here, we tested the impact of an IL-2 agonist in a novel model for food allergy to hen´s egg in mice sensitized without artificial adjuvants. Prophylactic IL-2 agonist treatment expanded Treg populations and inhibited allergen-specific sensitization. However, IL-2 agonist treatment of already sensitized mice increased mast cell responses and allergic anaphylaxis upon allergen re-challenge. These effects depended on allergen-specific IgE and were mediated through IFN-γ, as shown by IgE transfer and blockade of IFN-γ with monoclonal antibodies. These results suggest that although shifting the allergic reaction toward a Treg/Th1 response inhibits allergic sensitization, the prototypic Th1 cytokine IFN-γ promotes mast cell activation and allergen-induced anaphylaxis in individuals that are already IgE-sensitized. Hence, while a Th1 response can prevent the development of food allergy, IFN-γ has the ability to exacerbate already established food allergy.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Alaleh Rezalotfi ◽  
Ghasem Solgi ◽  
Marzieh Ebrahimi

Background. Gastrosphere, an enriched cellular population with stem-like properties believed to be responsible for an escape from immune-mediated destruction. Th17 and Treg cells play a major role in gastric cancer; however, their interaction with gastrospheres remained elusive. Method. Peripheral blood mononuclear cells were isolated from healthy donors and were cultured with conditioned media of MKN-45 (parental) cells as well as gastrospheres’ conditioned media in the context of mixed lymphocyte reaction and in the presence of anti-CD3/CD28 beads. The proliferation was evaluated using CFSE staining; the percentages of CD4+CD25+FoxP3+ Treg and CD4+IL-17+ Th17 cells and IFN-γ+cells and the production of IL-17, TGF-β, and IL-10 were assessed by flow cytometry and ELISA, respectively. Finally, the cytotoxic potential of induced immune cells was measured by examining the secretion of lactate dehydrogenase from target cells. Results. The results revealed a decreased expansion of PBMCs postexposure to gastrospheres’ conditioned medium which was concomitant with an increased percentage of Th17 and an enhanced Th17 to Treg ratio. The conditioned media of gastrospheres enhanced the secretion of IL-10 and IL-17 and decreased TGF-β. Interestingly, immune cells induced by gastrospheres showed significant cytotoxicity in terms of producing IFN-γ and death induction in target cells. All these changes were related to the upregulation of IL-6, IL-10, and IL-22 in gastrospheres compared to parental cells. Conclusion. Our study showed that the condition media of gastrospheres can potentially induce Th17 with increasing in their cytotoxic effect. Based on our knowledge, the present study is the first study that emphasizes the role of gastrospheres in the induction of antitumor Th17 cells. However, it should be confirmed with complementary studies in vivo.


Author(s):  
Esen Demir ◽  
Levent Midyat ◽  
Figen Gulen ◽  
Gulhadiye Akbas ◽  
Sema Tanrıverdi ◽  
...  

2018 ◽  
Vol 69 (9) ◽  
pp. 2541-2545
Author(s):  
Raluca Barzoi ◽  
Elena Rezus ◽  
Codruta Badescu ◽  
Razan Al Namat ◽  
Manuela Ciocoiu

There is a bidirectional interaction between most immune cells and osteoblasts, osteoclasts and their precursor cells. The receptor activator of nuclear factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) system plays an essential role in the formation of osteoblasts, but it also has implications in osteoclast biology and implicitly on the diseases characterized by bone loss. Proinflammatory cytokines existing at synovial level function as direct or indirect stimulators of osteoclast differentiation, but also of its survival or activity, although some cytokines may also play an antiosteocastogenic role. The fate of bone destruction is determined by the balance between osteoclastogenic and antiosteoclastogenic mediators. Our study has shown that the early initiation of the therapy with anti-TNF and anti-IL6 biological agents, in patients with rheumatoid arthritis, inhibits bone destruction, regardless of the anti-inflammatory activity in patients with rheumatoid arthritis.


2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali

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