Immunobiotics Research Group

San Miguel de Tucumán, Argentina

Immunobiotics Research Group

San Miguel de Tucumán, Argentina
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Tada A.,Immunobiotics Research Group | Tada A.,CONICET | Tada A.,Tohoku University | Zelaya H.,Immunobiotics Research Group | And 11 more authors.
Inflammation Research | Year: 2016

Objective: Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model. Results: Intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3+NK1.1+, CD3+CD8αα+, CD8αα+NKG2D+) and pro-inflammatory mediators (TNF-α, IL-1β, IFN-γ, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5, and RIG-I was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-α, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3+NK1.1+, CD3+CD8αα+, and CD8αα+NKG2D+ cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage. Conclusions: This work demonstrates the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains. © 2016, Springer International Publishing.


Zelaya H.,Immunobiotics Research Group | Zelaya H.,CONICET | Zelaya H.,National University of Tucuman | Tada A.,Tohoku University | And 14 more authors.
Inflammation Research | Year: 2015

Objective: To evaluate the effect of the nasal administration of live and heat-killed Lactobacillus rhamnosus CRL1505 (Lr1505) on immune-coagulative response during influenza virus (IFV) infection to improve survival and reduce lung injury. Methods: Six-week-old BALB/c mice were treated with live or heat-killed Lr1505 by the nasal route during two consecutive days. Treated and untreated control mice were then nasally challenged with IFV. Results: Both viable and non-viable Lr1505 protected infected mice by reducing pulmonary injury and lung viral loads trough several mechanisms: (a) Inflammatory cytokines were efficiently regulated allowing higher clearance of virus and reduction of inflammatory lung tissue damage, associated to higher levels of the regulatory cytokine IL-10. (b) The antiviral immune response was enhanced with improved levels of type I interferons, CD4+IFN-γ+ lymphocytes, and lung CD11c+CD11blowCD103+ and CD11c+CD11bhighCD103− dendritic cells. (c) The procoagulant state was reversed mainly by down-regulating tissue factor expression and restoring thrombomodulin levels in lung. The capacity of Lr1505 to improve the outcome of IFV infection would be related to its ability to beneficially modulate lung TLR3-triggered immune response. Conclusions: Our work is the first to demonstrate the ability of an immunobiotic strain to beneficially modulate inflammation–coagulation interactions during IFV infection. Interestingly, non-viable L. rhamnosus CRL1505 was as effective as the viable strain to beneficially modulate respiratory antiviral immune response. © 2015, Springer Basel.


Kitazawa H.,Tohoku University | Villena J.,Immunobiotics Research Group | Villena J.,CONICET
Frontiers in Immunology | Year: 2014

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants and young children. Host immune response is implicated in both protective and immunopathological mechanisms during RSV infection. Activation of Toll-like receptor (TLR)-3 in innate immune cells by RSV can induce airway inflammation, protective immune response, and pulmonary immunopathology. A clear understanding of RSV-host interaction is important for the development of novel and effective therapeutic strategies. Several studies have centered on whether probiotic microorganisms with the capacity to stimulate the immune system (immunobiotics) might sufficiently stimulate the common mucosal immune system to improve defenses in the respiratory tract. In this regard, it was demonstrated that some orally administered immunobiotics do have the ability to stimulate respiratory immunity and increase resistance to viral infections. Moreover, during the last decade scientists have significantly advanced in the knowledge of the cellular and molecular mechanisms involved in the protective effect of immunobiotics in the respiratory tract. This review examines the most recent advances dealing with the use of immunobiotic bacteria to improve resistance against viral respiratory infections. More specifically, the article discuss the mechanisms involved in the capacity of the immunobiotic strain Lactobacillus rhamnosus CRL1505 to modulate the TLR3-mediated immune response in the respiratory tract and to increase the resistance to RSV infection. In addition, we review the role of interferon (IFN)-γ and interleukin (IL)-10 in the immunoregulatory effect of the CRL1505 strain that has been successfully used for reducing incidence and morbidity of viral airways infections in children. © 2014 Kitazawa and Villena.


Zelaya H.,Immunobiotics Research Group | Zelaya H.,CONICET | Zelaya H.,National University of Tucuman | Tsukida K.,Tohoku University | And 12 more authors.
International Immunopharmacology | Year: 2014

The exacerbated disease due to immune- and coagulative-mediated pulmonary injury during acute respiratory viruses infection results in severe morbidity and mortality. Identifying novel approaches to modulate virus-induced inflammation-coagulation interactions could be important alternatives for treating acute respiratory viruses infections. In this study we investigated the effect of the probiotic strain Lactobacillus rhamnosus CRL1505 on lung TLR3-mediated inflammation, and its ability to modulate inflammation-coagulation interaction during respiratory viral infection. Our findings reveal for the first time that a probiotic bacterium is able to influence lung immune-coagulative reaction triggered by TLR3 activation, by modulating the production of proinflammatory and anti-inflammatory cytokines as well as expression of tissue factor and thrombomodulin in the lung. We also demonstrated that the preventive treatment with the probiotic bacteria beneficially modulates the fine tune balance between clearing respiratory viruses (respiratory syncytial virus and influenza virus) and controlling immune-coagulative responses in the lung, allowing normal lung function to be maintained in the face of a viral attack. Our data also pinpoint a crucial role for IL-10 in the immune protection induced by L. rhamnosus CRL1505 during respiratory viral infections. These observations might be helpful to propose new preventive or therapeutic approaches to better control virus-inflammatory lung damage using probiotic functional foods. © 2013 Elsevier B.V.


Villena J.,Immunobiotics Research Group | Villena J.,CONICET | Kitazawa H.,Tohoku University
Frontiers in Immunology | Year: 2014

The intestinal mucosa plays a critical role in the host's interactions with innocuous commensal microbiota and invading pathogenic microorganisms. Intestinal epithelial cells (IECs) and gut associated immune cells recognize the bacterial components via pattern-recognition receptors (PRRs) and are responsible for maintaining tolerance to the large communities of resident luminal bacteria while being also able to mount inflammatory responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs that are present on IECs and immune cells which are involved in the induction of both tolerance and inflammation. A growing body of experimental and clinical evidence supports the therapeutic and preventive application of probiotics for several gastrointestinal inflammatory disorders in which TLRs exert a significant role. This review aims to summarize the current knowledge of the beneficial effects of probiotic microorganisms with the capacity to modulate the immune system (immunobiotics) in the regulation of intestinal inflammation in pigs, which are very important as both livestock and human model. Especially we discuss the role of TLRs, their signaling pathways, and their negative regulators in both the inflammatory intestinal injury and the beneficial effects of immunobiotics in general, and Lactobacillus jensenii TL2937 in particular. This review article emphasizes the cellular and molecular interactions of immunobiotics with IECs and immune cells through TLRs and their application for improving animal and human health. © 2014 Villena and Kitazawa.


Villena J.,Immunobiotics Research Group | Villena J.,CONICET | Aso H.,Tohoku University | Kitazawa H.,Tohoku University
Frontiers in Immunology | Year: 2014

Intestinal epithelial cells (IECs) detect bacterial and viral associated-molecular-patterns (MAMPs) via germline-encoded pattern-recognition receptors (PRRs) and are responsible for maintaining immunetolerance to the communities of resident commensal bacteria while being also capable to mount immune responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs expressed on IECs and immune cells, which are involved in the induction of both tolerance and inflammation. In the last decade, experimental and clinical evidence was generated to support the application of probiotics with immunoregulatory capacities (immunobiotics) for the prevention and treatment of several gastrointestinal inflammatory disorders in which TLRs exert a significant role. The majority of these studies were performed in mouse and human cell lines and, despite the growing interest in the bovine immune system due to the economic importance of cattle as livestock, only few studies have been conducted on cattle. In this regard, our group have established a bovine intestinal epithelial (BIE) cell line originally derived from fetal bovine intestinal epitheliocytes and used this cell line to evaluate the impact of immunobiotics in TLR mediated inflammation. This review aims to summarize the current knowledge of the beneficial effects of immunobiotics in the regulation of intestinal inflammation/infection in cattle. Especially we discuss the role of TLRs and their negative regulators in both the inflammatory response nd the beneficial effects of immunobiotics in bovine IECs. This review article emphasizes the cellular and molecular interactions of immunobiotics with BIE cells through TLRs and gives the scientific basis for the development of immunomodulatory feed for bovine healthy development. © 2014 Villena, Aso and Kitazawa.


PubMed | Immunobiotics Research Group and Tohoku University
Type: Journal Article | Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] | Year: 2016

Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model.Intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3(+)NK1.1(+), CD3(+)CD8(+), CD8(+)NKG2D(+)) and pro-inflammatory mediators (TNF-, IL-1, IFN-, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5, and RIG-I was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3(+)NK1.1(+), CD3(+)CD8(+), and CD8(+)NKG2D(+) cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage.This work demonstrates the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains.


Salva S.,Immunobiotics Research Group | Salva S.,CONICET | Marranzino G.,Immunobiotics Research Group | Marranzino G.,CONICET | And 7 more authors.
International Immunopharmacology | Year: 2014

This work evaluated the capacity of two probiotic strains, Lactobacillus casei CRL431 and Lactobacillus rhamnosus CRL1506, to protect against myelosuppression and immunosuppression in cyclophosphamide (Cy)-treated mice. Changes in mature granulocytes and progenitor cells in bone marrow (BM) and blood were studied. In addition, the ability of probiotics to accelerate the recovery of the immune response against the opportunistic pathogen Candida albicans was evaluated. We demonstrated for the first time that the preventive treatment with immunomodulatory lactobacilli such as L. casei CRL431 or L. rhamnosus CRL1506 was able to increase immature myeloid progenitors in the BM, allowing an early recovery of myeloid cells after Cy administration. Probiotic lactobacilli were also capable to induce an early recovery of neutrophils in blood, improve phagocytic cells recruitment to infectious sites and increase the resistance against the opportunistic pathogen C. albicans. Although deeper studies regarding the cellular and molecular mechanisms of probiotic actions are needed, these findings support the idea that strains like CRL431 and CRL1506 may accelerate the recovery of Cy-caused immunosuppression by immunopotentiating myeloid cells. Then, probiotic lactobacilli have the potential to be used as alternatives for lessening chemotherapy-induced immunosuppression in cancer patients. © 2014 Elsevier B.V.


Zelaya H.,Immunobiotics Research Group | Zelaya H.,National University of Tucuman | Villena J.,Immunobiotics Research Group | Villena J.,CONICET | And 7 more authors.
Microbiology and Immunology | Year: 2014

The present study evaluated the effect of nasally given Lactobacillus rhamnosus CRL1505 on the immunocoagulative response during pneumococcal infection in immunocompetent mice. In addition, we aimed to gain insight into the mechanism involved in the immunomodulatory effect of the L. rhamnosus CRL1505 strain by evaluating the role of TLR2. Results showed that nasally given L. rhamnosus CRL1505 effectively regulates inflammation and hemostatic alterations during the pneumococcal infection. Immunobiotic treatment significantly reduced permeability of the bronchoalveolar-capillary barrier, and general cytotoxicity, decreasing lung tissue damage. The CRL1505 strain improved the production of TNF-α, IFN-γ, and IL-10 after pneumococcal challenge. In addition, increased TM and TF expressions were found in lungs of L. rhamnosus CRL1505-treated mice. Moreover, we demonstrated, for the first time, that the TLR2 signaling pathway has a role in the induction of IFN-γ and IL-10 and in the reduction of TF. The results also allow us to speculate that a PRR, other than TLR2, may mediate the immunobiotic activity of L. rhamnosus CRL1505 and could explain changes in TNF-α and TM. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.


PubMed | Immunobiotics Research Group
Type: Journal Article | Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] | Year: 2015

To evaluate the effect of the nasal administration of live and heat-killed Lactobacillus rhamnosus CRL1505 (Lr1505) on immune-coagulative response during influenza virus (IFV) infection to improve survival and reduce lung injury.Six-week-old BALB/c mice were treated with live or heat-killed Lr1505 by the nasal route during two consecutive days. Treated and untreated control mice were then nasally challenged with IFV.Both viable and non-viable Lr1505 protected infected mice by reducing pulmonary injury and lung viral loads trough several mechanisms: (a) Inflammatory cytokines were efficiently regulated allowing higher clearance of virus and reduction of inflammatory lung tissue damage, associated to higher levels of the regulatory cytokine IL-10. (b) The antiviral immune response was enhanced with improved levels of type I interferons, CD4(+)IFN-(+) lymphocytes, and lung CD11c(+)CD11b(low)CD103(+) and CD11c(+)CD11b(high)CD103(-) dendritic cells. (c) The procoagulant state was reversed mainly by down-regulating tissue factor expression and restoring thrombomodulin levels in lung. The capacity of Lr1505 to improve the outcome of IFV infection would be related to its ability to beneficially modulate lung TLR3-triggered immune response.Our work is the first to demonstrate the ability of an immunobiotic strain to beneficially modulate inflammation-coagulation interactions during IFV infection. Interestingly, non-viable L. rhamnosus CRL1505 was as effective as the viable strain to beneficially modulate respiratory antiviral immune response.

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