Are the immunomodulatory properties of Lactobacillus rhamnosus CRL1505 peptidoglycan common for all Lactobacilli during respiratory infection in malnourished mice?

Previously, we reported that Lactobacillus rhamnosus CRL1505 peptidoglycan (PG05) improves the innate immune response in immunocompromised-malnourished mice after Streptococcus pneumoniae infection. This study extends those previous findings by demonstrating that the dietary recovery of malnourished mice with nasal administration of PG05 improves not only the innate immune response but the respiratory and systemic adaptive humoral response as well. PG05 enhanced the Th2 response, the recovery of B cells, and the concentration and opsonophagocytic activity of anti-pneumococcal antibodies. In addition, by performing comparative studies with the peptidoglycans from lactobacilli of the same species (L. rhamnosus CRL534) or with similar immunomodulatory properties (L. plantarum CRL1506), we demonstrated here that PG05 has unique immunomodulatory properties that cannot be extended to peptidoglycans from other probiotic strains. However, the knowledge of the molecular characteristics of PG05 is indispensable to understand immunomodulatory abilities of L. rhamnosus CRL1505.Fil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

The role of immunobiotics and postbiotics in the recovery of immune cell populations from respiratory mucosa of malnourished hosts: effect on the resistance against respiratory infections

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobiotic Lactobacillus rhamnosus CRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to other L. rhamnosus or probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today.Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Ivir, Héctor Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Gutiérrez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. 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; Argentin

Alterations of blood immune cells in COVID-19 elderly patients with or without type 2 diabetes

Elderly individuals, especially those with pre-existing conditions like diabetes mellitus (DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alterations of blood immune cells (BIC) in patients with symptomatic COVID-19 and confirmed SARS-CoV-2 infection, ≥ 60 years and who needed hospitalization in the Centro de Salud Hospital of Tucuman during the second peak of the pandemic. Blood samples were taken at the time of admission (d0) and five days after (d5) for routine laboratory tests and the characterization of BIC by flow cytometry. Most of the patients were men (70%) aged between 60 and 78 years. The 70% of patients had DM while 50% had arterial hypertension. At d0, all the patients had increased neutrophils and inflammatory markers (C reactive protein and D-dimers) and reduced numbers of lymphocytes, HLA-DRhi monocytes, CD16+CD56+ NK cells, CD3+HLA-DR+CD25+ cells, CD4+ and CD8+ T cells in blood. Patients received a standard treatment for COVID-19 care (O2, corticosteroids and antibiotics). The treatment normalized the levels of BIC (d5) in 30% of patients who were those with no comorbidities. In patients with DM, BIC recovery was variable. In DM patients who required administration of plasma (30%), prolonged O2 therapy (40%) or referral to the intensive care unit (10%) significant reductions of CD16+CD56+, CD3+HLA-DR+CD25+, CD4+ and CD8+ cells were observed between d0 and d5. In line with previous studies, our results shows that absolute counts of major lymphocyte subsets in blood are significantly and substantially decreased during the course of severe COVID-19 disease in elderly patients. These BIC alterations may persist despite clinical care in elderly patients with DM. Further studies are needed to investigate the utility of early lymphocyte subset measurements as prognostic biomarkers of disease severity, mortality, and response to treatment in COVID-19 elderly patients with DM.Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán; ArgentinaFil: Argañaraz, Nicolás. Universidad Nacional de Tucumán; ArgentinaFil: Rocchia Novillo, María Pía. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hosp. Centro de Salud "zenon Santillan"; ArgentinaFil: Rocchia Novillo, María del Milagro. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hosp. Centro de Salud "zenon Santillan"; ArgentinaFil: Albarracin, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Charubi, Jacqueline Elizabeth. Instituto de Maternidad “Ntra. Sra. De las Mercedes”; ArgentinaFil: Casen, Alejandra. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hosp. Centro de Salud "zenon Santillan"; ArgentinaFil: Gobbato, Nadia Margarita. Universidad Nacional de Tucumán; ArgentinaFil: Rachid, Mirta Maria. Universidad Nacional de Tucumán; ArgentinaFil: Alvarez, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Valdéz, Juan Carlos. Universidad Nacional de Tucumán; ArgentinaAnnual Meeting of Bioscience Societies 2021: LXVI Annual Meeting of Sociedad Argentina de Investigación Clínica (SAIC), LXIX Annual Meeting of Sociedad Argentina de Inmunología(SAI), LIII Annual Meeting of Asociación Argentina de Farmacología Experimental (AAFE), XI Annual Meeting of Asociación Argentina de Nanomedicinas (NANOMED-Ar)Buenos AiresArgentinaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de Investigación ClínicaAsociación Argentina de Nanomedicin

Evaluación de las propiedades adyuvantes de fracciones celulares de bacterias inmunobióticas para el diseño de nuevas formulaciones vacunales contra Streptococcus pneumoniae

Streptococcus pneumoniae (neumococo) representa uno de los mayores problemas de salud a nivel mundial debido a que es causa común de infecciones del tracto respiratorio y enfermedades invasivas especialmente en grupos de alto riesgo como niños en sus primeros años de vida, adultos y pacientes inmunocomprometidos. La emergencia de cepas de neumococos multiresistentes en el mundo ha conducido a un incremento en la necesidad de la prevención de infecciones por S. pneumoniae mediante la vacunación. Sin embargo, la vacunas disponibles para su aplicación en humanos todavía tienen las desventajas asociadas con su reducida inmunogenicidad y la baja memoria inmunológica en las poblaciones de alto riesgo como los niños (i.e. vacunas de polisacáridos de neumococos) o con su elevado costo como estrategia de salud pública en comunidades de escasos recursos (i.e. vacunas conjugadas) . Por lo tanto, los actuales esfuerzos en el desarrollo de vacunas para neumococo se focalizan en la exploración de estrategias alternativas que permitan mejorar la eficacia y efectos de las formulaciones existentes. Con el objeto de mejorar la eficiencia de las vacunas, es necesario incluir nuevos tipos de adyuvantes, capaces de estimular a las células presentadoras de antígenos, induciendo la producción de citoquinas que favorezcan la presentación antigénica, la producción de anticuerpos específicos y la mejora de la memoria inmunológica. Entre estos tipos de adyuvantes, se encuentran componentes de origen bacteriano, capaces de estimular los receptores de reconocimiento de patrones (PRR), como por ejemplo el receptor de tipo Toll-2 (TLR2). Previamente, hemos demostrado que tanto Lactobacillus rhamnosus CRL1505 no viable como sus fracciones celulares (pared celular y péptidoglicano) tienen la capacidad de inducir una mejor respuesta inmune innata a nivel sistémico y respiratorio en animales desnutridos, al ser administrados por vía nasal u oral. Sin embargo, hasta el momento, no se ha evaluado la capacidad de sus fracciones celulares, empleadas como adyuvantes de vacunas de administración nasal, para conferir inmunidad protectora en poblaciones de riesgo. Por lo tanto, en este trabajo evaluamos si las fracciones celulares provenientes de la cepa inmunomoduladora L. rhamnosus CRL1505 pueden ser empleadas como adyuvantes de mucosa efectivos para la mejora de la eficiencia de la inmunización en ratones infantes. Más aún, estudiamos si la inmunización de ratones albino Suizos infantes con las fracciones celulares son capaces de mejorar la resistencia al patógeno respiratorio.Streptococcus pneumoniae is a major global health problem in high-riskgroups. Even when vaccines are available, they show reduced low immunological memory in these populations. Other disadvantageis the high cost as a public health strategy in communities with low incomes. Inthis context, immunobiotic bacteria such as Lactobacillus rhamnosus CRL1505 or its cellular fractions could represent candidates as mucosal adjuvant. Theaim of this work was to study the potential use of cell wall (PC) or peptidoglycan(PG) from the immunomodulatory strain L. rhamnosus CRL1505, aseffective mucosal adjuvant in infant and adult mice when are co-administered with the commercially available conjugated-polysaccharide 13-valent pneumococcal vaccine (Vc). Results showed that administration of the Vc induced production of pneumococcal-specific antibodies in serum and broncho-alveolarlavage (BAL) in adult and infant mice. Infant mice showed higher levels of specific IgM and IgA in serum, and specific IgA and IgG in BAL, respectto adults after nasal immunization. In addition, subcutaneous immunization induced higher antibody levels in adults than infant mice. Co-administrationof Vc+PC or Vc+PG induced higher pneumococcal-specific antibodies (IgM,IgA, IgG) compared to Vc alone in infant mice. To evaluate the capability of Vcand cell fractions to protect from infection, four S. pneumoniae serotypes (3,6B, 14, and 19F) were used. Only the nasal immunization with Vc+PC significantlyreduced the pneumococcal lung colonization by the 4 serotypes, whilethe combination Vc+PG reduced lung colonization by serotype 3 and 6B, withno effect on serotypes 14 and 19F. All treatments (Vc, Vc+PC, and Vc+PG) avoided pathogen dissemination into blood. The results suggest that cell wallfrom L. rhamnosus CRL1505 is an interesting and potential mucosal adjuvantto improve effectiveness of commercial vaccines and increasing protection in children.Fil: Laiño, Jonathan Emiliano. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Aguero Villoldo, Maria Graciela. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Non-viable immunobiotic Lactobacillus rhamnosus CRL1505 and its peptidoglycan improve systemic and respiratory innate immune response during recovery of immunocompromised-malnourished mice

The effect of non-viable Lactobacillus rhamnosus CRL1505 and its cell wall and peptidoglycan on respiratory immunity in malnourished mice was studied.Weaned mice were malnourished with a protein-free diet for 21d and received BCD during 7d (BCD) or BCD with nasal non-viable L. rhamnosus CRL1505 (BCD + UV) or its cell wall (BCD + CW) or peptidoglycan (BCD + PG) supplementation during last 2d of the treatment. Malnourished mice without treatment (MNC) and well-nourished mice (WNC) were used as controls. Mice were infected nasally with Streptococcus pneumoniae after treatments. Resistance against pneumococci was reduced in MNC mice.Repletion with BCD reduced lung and blood bacterial cell counts when compared to MNC mice but the counts did not reach the levels of the WNC group. However, when malnourished mice received BCD + UV, BCD + CW or BCD+PG, pneumococci was not detected in lung or blood samples. Pneumococcal infection increased the levels of TNF-α, IL-1β, IL-6, and IL-10 in the respiratory tract, however the values were lower in MNC than in WNC mice.BCD + UV and BCD + PG groups showed values of phagocytes, IL-1β and IL-6 that were similar to WNC mice,while TNF-α was significantly higher in those groups when compared to WNC mice. Moreover, BCD + UV and BCD+PG treatments improved levels of respiratory IL-10, reaching values that were superior to those observed in WNC mice. The work demonstrates for the first time that non-viable probiotic bacteria or their cellular fractions could be an interesting alternative as mucosal mmunomodulators, especially in immunocompromised hosts in which the use of live bacteria might be dangerous.Fil: Kolling, Yanina Noralí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Marranzino, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentin