Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus sonchifolius) root flour in an intestinal infection model with Salmonella Typhimurium

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50 – 70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up- regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immu- nomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1aþ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.Fil: Velez, Eva Maria del Mar. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Castillo, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Mesón, Oscar Enrique. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Grau, Alfredo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Laboratorio de Investigaciones Ecológicas de las Yungas; ArgentinaFil: Bibas Bonet, María Eugenia. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; ArgentinaFil: Perdigón, Gabriela del Valle. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

The Low Incidence of Viral Hepatitis Reactivation Among Subjects on Immunotherapy Reduces the Impact of Suboptimal Screening Rate

Cancer; Checkpoint inhibitors; Hepatitis BCáncer; Inhibidores del punto de control; Hepatitis BCàncer; Inhibidors del punt de control; Hepatitis BBackground and Aims: Immunotherapy with immune checkpoint inhibitors (ICIs) is a pillar of many advanced tumors. However, there is scarce data concerning the rate of viral hepatitis screening in this population or the risk of viral reactivation. Methods: Retrospective–prospective study that includes all patients who began ICIs between January/2019 and December/2020 in a University Hospital. Data on viral hepatitis screening prior to the beginning of ICIs were collected. In subjects lacking information, serological tests were requested prospectively. Among HBsAg, anti-HBc, or anti-HCV positive subjects, reactivation was prospectively assessed. Results: During the 2-year period of study, 595 subjects received ICIs (61.2% male, mean age 63 years). The most prevalent cancers found were 35.5% lung cancer, 12.1% melanoma, and 8.2% head and neck; ICIs schemes were mainly anti-PD1 (65.7%), followed by anti-PD-L1 (19.2%), and combined therapy (13.6%). Prior to immunotherapy, anti-HCV screening was performed in 462 (77.6%) subjects, HBsAg in 462 (77.6%), anti-HBc in 335 (56.3%), and the complete screening in 328 (55.1%). The anti-HBc screening was more frequently ordered among patients treated with concomitant systemic therapy (p = 0.003), especially in the case of chemotherapy (p = 0.015), though HCV screening was more commonly performed in concomitant therapies different from chemotherapy (p = 0.001). Serological tests were completed prospectively in those alive, leading to an overall prevalence for anti-HCV of 3.5%, HBsAg at 1.3%, and anti-HBc of 15.2%. HCV-RNA was detected in 2/19 (both patients with hepatocellular carcinoma), HBV-DNA in 4/7 HBsAg positive, and in 1/75 anti-HBc positive subject. Five out of the 7 HBsAg carriers and 1/75 anti-HBc+ subjects (due to concomitant antiretroviral therapy) received antiviral prophylaxis. Neither cases of HBV reactivation nor changes in HCV viral load were observed. Discussion: HBV and HCV screening prior to immunotherapy is suboptimal. Though the rate of viral hepatitis reactivation seems extremely low, efforts should be made to optimize viral hepatitis screening prior to immunotherapy for the selection of candidates for either antiviral prophylaxis or periodical follow-up

Long-term analysis of antibodies elicited by SPUTNIK V: A prospective cohort study in Tucumán, Argentina

Background: Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in nay¨ve and previously infected volunteers who received SPUTNIK V. Methods: Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucuman, Argentina. Findings: Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on postvaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). Interpretation: Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred.Fil: Chahla, Rossana Elena. Ministerio de Salud Pública de Tucumán; ArgentinaFil: Tomas Grau, Rodrigo Hernán. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Ploper, Diego. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Vera Pingitore, Esteban. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Aguilar López, Mónica. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Aznar, Patricia. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Alcorta, María Elena. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Velez, Eva Maria del Mar. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Stagnetto, Agustín. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Avila, Cesar Luis. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Socias, Sergio Benjamin. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Heinze, Dar. University Of Boston. School Of Medicine. Center For Regenerative Medicine.; Estados UnidosFil: Navarro, Silvia Adriana. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Llapur, Conrado Juan. Ministerio de Salud Pública de Tucumán; ArgentinaFil: Costas, Dardo. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Flores, Isolina. Gobierno de la Provincia de Tucuman. Ministerio de Salud. Departamento Bioquimico. Laboratorio de Salud Publica.; ArgentinaFil: Edelstein, Alexis. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Kowdle, Shreyas. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Apfelbaum, Gabriela. Universidad Nacional de Tucumán; ArgentinaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Mostoslavsky, Gustavo. University Of Boston. School Of Medicine. Center For Regenerative Medicine.; Estados UnidosFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Chehin, Rosana Nieves. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentin

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

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 specificIgE, 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.Fil: Velez, Eva Maria del Mar. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Weil, R.. Universidad Isalud; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Immune modulation promoted by probiotic fermented milk in the mucosal immune system in an experimental model of allergy

Intestinal microbiota has an essential role in the maturation and function of the immune system. Changes in the microbiota, together withgenetic factors induce the development of allergy with a typical Th2 profile(1). Several studies have shown that probiotics have a beneficialeffect in disease and can stimulate the mucosal immune system by improving microbiota composition(2); hence, probiotics oral admin-istration is proposed to avoid the allergy development by balancing microbiota and modulating the immune system, not only at theintestinal mucosa, but also in other mucosal sites and at systemic level(3). This study was aimed to evaluate the adjuvant immune effect ofthe oral administration of a probiotic fermented milk (PFM) in the intestinal mucosa and the extent of these effects on distant mucosalsites (bronchus) in an experimental mouse model of allergic airway reactivity to ovoalbumin (OVA). Experimental groups: normal-control(NC), Basal (B-5days-PFM); OVA-Sensitization-control (SC), Previous (P) (5d-PFM +OVA +H2O) and Continuous (C) (5d-PFM +OVA +PFM). SC, P and C were sensitized with OVA 1 % followed by daily exposures to OVA aerosols. At 7 and 15 days post-sensitization (dPS) specific-IgE, specific-IgG and IL-10 in serum, total S-IgA, IL-10 and IFN-gin intestinal fluid (IF), specific-IgE inbronchoalveolar lavage (BAL) were determined by ELISA. The number of IgA +, IL-10 +and IL-4 +cells in the lamina propria of smallintestine (SI) and lungs were determined by immunofluorescense assay. In large intestine (LI) total populations of total anaerobes,lactobacilli, bifidobacteria and enterobacteria in selective media were determined. Specific-IgE was reduced in treated groups with regardto SC in serum and BAL (DO 450nm) (Table 1). Specific-IgG increased in all groups but showed the highest values in C (Table 2).Table 1. Anti OVA IgE in serum (Absorbance, DO 450 nm) (media°SD)NC B SC P C5 dPFM 0.08°0.01 0.09°0.017 dPS 0.87°0.07 0.38°0.13 0.38°0.01215 dPS 0.47°0.02 0.47°0.01 0.31°0.06Table 2. Anti OVA IgG in serum (Absorbance, DO 450 nm) (media°SD)NC B SC P C5 dPFM 0.06°0.01 0.08°0.037 dPS 0.78°0.01 0.80°0.05 1,03°0.0715 dPS 0.67°0.06 0.65°0.13 0.92°0.10IL-10 values increased in SC in SI fluid compared to treated groups, with no changes in serum. Total S-IgA from SI fluid significantlyincreased in CS and P compared to NC, B and C. IL-4 +cells increased significantly in SC in lungs compared to the other groups at 7 and15 dPS; in SI no differences were found between controls and treated groups. The number of IL-10 +cells was significantly higher in thelamina propria of SI from SC group compared to P and C at 7 and 15 dPS. PFM induced a decrease of enterobacteria and increase ofbifidobacteria only in C, other populations were not affected. PFM reduced specific-IgE levels in serum and BAL in mice with continuoustreatment; this could be mediated by intestinal microbiota regulation that might have influence on the expression of cytokines IL-4(Th2 type) and IL-10 (regulatory cytokine) at the mucosal level (intestine and lungs). However systemic and mucosal normal immuneresponse was not affected because IgG and S-IgA production was not altered by IL-10.1. Bjorksten B, Sepp E, Julge K et al. (2001) J Allergy Clin Immunol 108, 516?520.2. Galdeano CM & Perdigon G (2006) Clin Vaccine Immunol 13, 219?226.3. de Moreno de LeBlanc A, Maldonado Galdeano C, Chaves, S and Perdigon, G. (2005) Eur J Inflamm 3, 25?30.Fil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Maldonado, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; ArgentinaFil: Carmuega, E.. Nutritia; ArgentinaFil: Weil, R.. DANONE; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentin

Sistema inmune de las mucosas: Influencia bacteriana en la activación y homeostasis intestinal

1.La inmunidad de mucosa intestinal opera en tejidos como mecanismo de defensa biológica para eliminar microorganismos patógenos invasores, además de actuar como mecanismo para el mantenimiento de la homeostasis. 2.Las células epiteliales intestinales (CEIs), por su ubicación son cruciales para el reconocimiento inicial de moléculas extrañas y para la generación de señales que se transmiten a las células inmunocompetentes del tejido subyacente. 3.Bacterias no patógenas llamadas probióticos, toman directamente contacto con las CEIs y como consecuencia se inicia una cascada de señales con marcada influencia en las células inmunes asociadas a intestino.Fil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Lemme Dumit, José María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

ImmunoteràpiaInmunoterapiaImmunotherapyCancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities.This work was supported by the Spanish Melanoma Group (GEM)

Study of the mechanisms exerted by fructooligosaccharides from Yacon in an intestinal infection model

Fructooligosacharides (FOS), obtained from Yacon roots, have a prebiotic effect when used as a dietary supplement. We studied if FOS from Yacón can prevent enteric infection against Salmonella Typhimurium and the mechanism involved. BALB/c mice were divided into 4 groups: normal control, Basal (45days with FOS-340mg/kg/day), infection control (IC?without FOS administration) and treated group (TG?45d with FOS+S. Typhimurium); IC and TG groups were challenged at days 15, 30 and 45 with S. Typhimurium. Translocation to liver and spleen, total and specific s-IgA, IgA+, TLR4+, CD206+, IL6+, TNFalfa, IFNgamma and MIP 1alfa + cells were analyzed after challenge. We found protection only at 30 days of FOS administration with an increase in the total s-IgA but not in the specific s-IgA levels for TG compared with IC group. In TG as regard IC group the N° IgA+, TLR4+, CD206+, IL6+ and MIP 1alfa+, TNFalfa and IFNgamma cells were increased. We demonstrate that FOS from Yacón roots prevent S. Typhimurium infections up to 30 days of administration through non-specific immunity with increased total s-IgA, expression of TLR4 and CD206 receptors and IL6+ and MIP1alfa + cells, that would improve immunological barrier mechanisms against S. Typhimurium infection.Fil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Castillo, Natalia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Mesón, Oscar Enrique. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Grau, Alfredo. Universidad Tecnológica Nacional; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina15th International Congress of Mucosal ImmunologyParisFranciaUniversidad de París Descarte

Beneficial effects of probiotic consumption on the immune system

Background: The gastrointestinal tract is one of the most microbiologically active ecosystems that plays a crucial role in the working of the mucosal immune system (MIS). In this ecosystem, the consumed probiotics stimulate the immune system and induce a network of signals mediated by the whole bacteria or their cell wall structure. This review is aimed at describing the immunological mechanisms of probiotics and their beneficial effects on the host. Summary: Once administered, oral probiotic bacteria interact with the intestinal epithelial cells (IECs) or immune cells associated with the lamina propria, through Toll-like receptors, and induce the production of different cytokines or chemokines. Macrophage chemoattractant protein 1, produced by the IECs, sends signals to other immune cells leading to the activation of the MIS, characterized by an increase in immunoglobulin A + cells of the intestine, bronchus and mammary glands, and the activation of T cells. Specifically, probiotics activate regulatory T cells that release IL-10. Interestingly, probiotics reinforce the intestinal barrier by an increase of the mucins, the tight junction proteins and the Goblet and Paneth cells. Another proposed mechanism of probiotics is the modulation of intestinal microbiota by maintaining the balance and suppressing the growth of potential pathogenic bacteria in the gut. Furthermore, it has been demonstrated that long-term probiotics consumption does not affect the intestinal homeostasis. The viability of probiotics is crucial in the interaction with IECs and macrophages favoring, mainly, the innate immune response. Macrophages and Dendritic cells (DCs) play an important role in this immune response without inducing an inflammatory pattern, just a slight increase in the cellularity of the lamina propria. Besides, as part of the machinery that probiotics activate to protect against different pathogens, an increase in the microbicidal activity of peritoneal and spleen macrophages has been reported. In malnutrition models, such as undernourishment and obesity, probiotic was able to increase the intestinal and systemic immune response. Furthermore, probiotics contribute to recover the histology of both the intestine and the thymus damaged in these conditions. Probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. Different mechanisms such as the generation of cytokines from activated pro-T-helper type 1, which favor the production of IgG instead of IgE, have been proposed. Key Messages: Probiotic bacteria, their cell walls or probiotic fermented milk have significant effects on the functionality of the mucosal and systemic immune systems through the activation of multiple immune mechanisms.Fil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Cazorla, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Lemme Dumit, José María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología. Cátedra de Inmunología; Argentin

Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisationprocess. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treatingallergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed withPFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and15 Q5 IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-g (IFN-g), IL-4, IL-10 and total S-IgA were measured in the supernatants of macerated lungs or in the BALF. The levels of IgAþ, CD4þ and CD8þ Q6 T lymphocytes and F4/80þ cells were measured in the lungs by immunofluorescence. Inducible CD4þ/CD25/Foxp3þ 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-g that play an important role in immunomodulation exerted by PFM admin- istration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels ofanti-OVA-specific IgG and total S-IgA. PFM did not influence Treg cells 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 Th1instead of the direct activation of Th2 cells to produce IgE.Fil: Velez, Eva Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Maldonado Galdeano, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; ArgentinaFil: Carmuega, Esteban. Centro de Estudios Nutricionales Infantiles; ArgentinaFil: Weill, Ricardo. DANONE; ArgentinaFil: Bibas Bonet, María Eugenia. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; ArgentinaFil: Perdigon, Gabriela del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Microbiología; Argentin