The Modulation of Mucosal Antiviral Immunity by Immunobiotics: Could They Offer Any Benefit in the SARS-CoV-2 Pandemic?

Viral respiratory infections are of major importance because of their capacity to cause of a high degree of morbidity and mortality in high-risk populations, and to rapidly spread between countries. Perhaps the best example of this global threat is the infectious disease caused by the new SARS-CoV-2 virus, which has infected more than 4 million people worldwide, causing the death of 287,000 persons according to the WHO's situation report on May 13, 2020. The availability of therapeutic tools that would be used massively to prevent or mitigate the detrimental effects of emerging respiratory viruses on human health is therefore mandatory. In this regard, research from the last decade has reported the impact of the intestinal microbiota on the respiratory immunity. It was conclusively demonstrated how the variations in the intestinal microbiota affect the responses of respiratory epithelial cells and antigen presenting cells against respiratory virus attack. Moreover, the selection of specific microbial strains (immunobiotics) with the ability to modulate immunity in distal mucosal sites made possible the generation of nutritional interventions to strengthen respiratory antiviral defenses. In this article, the most important characteristics of the limited information available regarding the immune response against SARS-CoV-2 virus are revised briefly. In addition, this review summarizes the knowledge on the cellular and molecular mechanisms involved in the improvement of respiratory antiviral defenses by beneficial immunobiotic microorganisms such as Lactobacillus rhamnosus CRL1505. The ability of beneficial microorganisms to enhance type I interferons and antiviral factors in the respiratory tract, stimulate Th1 response and antibodies production, and regulate inflammation and coagulation activation during the course of viral infections reducing tissue damage and preserving lung functionally, clearly indicate the potential of immunobiotics to favorably influence the immune response against SARS-CoV-2 virus.Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Kitazawa, Haruki. Tohoku University

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

Respiratory antiviral immunity and immunobiotics: Beneficial effects on inflammation-coagulation interaction during influenza virus infection

Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation-coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.Fil: Zelaya, María Hortensia del Rosario. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentin

Immunobiotics beneficially modulate TLR4 signaling triggered by lipopolysaccharide and reduce hepatic steatosis in vitro

Hepatic inflammation and injury may result from the translocation of pathological bacteria and their proinflammatory mediators. Probiotics attenuate hepatic diseases related to inflammation by exhibiting immunoregulatory effects. Therefore, this study was conducted to evaluate lipid reduction and immunoregulatory potentials of probiotic bacteria in vitro. HepG2 cells treated with total cellular fluid (TCF) of LABs reduced lipid accumulation. Moreover, cells responded to lipopolysaccharide (LPS) by producing higher levels of IL-6, IL-8, MCP-1, and TNF-α. TCF of LABs treatment showed remarkably diminished levels of the expression of these cytokines via modulation of the expression of TLR-negative regulators, as well as MAPK and NF-κB pathways. Moreover, heat-killed LABs were able to diminish TGF-β, IL-1β, and IL-6 and to increase IL-10 and TLR4 levels in THP-1 cells. LABs also decreased the protein level of TNF-α. These results demonstrated that immunobiotics exhibit potent immunoregulatory activity and may be used as effective therapeutic agents to alleviate inflammatory response.Fil: Kanmani, Paulraj. Dongguk University; Corea del SurFil: Ansari, AbuZar. Dongguk University; Corea del SurFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kim, Hojun. Dongguk University; Corea del Su

Editorial: Nutrition, Immunity and Viral Infections

Viral infectious diseases have a great impact on humankind. Pandemic, epidemic, and endemic viral diseases produce considerable morbidity and mortality, negatively affecting not only health and well-being but also local and global economies by increasing school and work absenteeism as well as the healthcare system expenses. Probably the best example of this global threat is the infectious disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has infected millions of people globally during the 2019-2020 pandemic [WHO, coronavirus pandemic; (1)]. Viral infections not only affect the economy in terms of human life, they also induce losses in livestock and crops (2), and can break down the barriers between animals and people, creating new potential dangers to human health (3). The SARS-CoV-2 pandemic pushed healthcare systems around the world to the limit and put pressure on the scientific community to provide solutions that help to prevent or alleviate its harmful effects. In consequence, in the past few months, there has been a reevaluation of the work of scientists actively investigating the biological features of viral infections, as well as potential preventive and therapeutic tools to combat them.Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Shimosato, Takeshi. Shinshu University; JapónFil: Vizoso Pinto, María Guadalupe. 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; ArgentinaFil: Kitazawa, Haruki. Tohoku University; Japó

Draft genome sequence of Lactobacillus plantarum CRL1506, an immunomodulatory strain isolated from goat milk

This report describes a draft genome sequence of Lactobacillus plantarum CRL1506, a probiotic strain with immunomodulatory properties isolated from goat milk. The reads generated by a whole-genome shotgun (WGS) strategy on an Illumina MiSeq sequencer were assembled into contigs with a total size of 3,228,096 bp. The draft genome sequence of L. plantarum CRL1506 will be useful for further studies of specific genetic features of this strain and for understanding the mechanisms of its immunobiotic properties.Fil: Saavedra, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Hebert, Elvira Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University; JapónFil: Salva, Maria Susana. 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; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Tohoku University; Japó

Recent advances and future perspective in microbiota and probiotics

Recent studies have highlighted the critical 1 role of intestinal microbes on health. This special issue covers a range of diverse topics related to microbiota and probiotic in gut health and disease, thus highlighting the potential beneficial role friendly bacteria in human health. We hope the papers published will serve to further highlight the potential application of probiotics for the prevention and treatment of gut diseases, as well as stimulating further research into the cellular and molecular mechanisms of probiotic actions.Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science; JapónFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Suvorov, Alexander. Institute of Experimental Medicine; RusiaFil: Melnikov, Vyacheslav. International Science and Technology Center; RusiaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Sánchez, Borja . Consejo Superior de Investigaciones Cientificas; Españ

Probiotics for everyone! The novel immunobiotic lactobacillus rhamnosus CRL1505 and the beginning of social probiotic programs in Argentina

Lactobacillus rhamnosus CRL1505 (Lr1505) stimulates immune responses in the gut and in the respiratory tract and improves resistance against Salmonella typhimurium and Streptococcus pneumoniae infections in immunocompetent and immunocompromised mice. Considering that respiratory infectious diseases continue to be a major cause of death among preschool children in developing countries, the aim of the present study was to evaluate the effect of Lr1505 on the health of children. A randomized-controlled double-blind clinical trial in 298 healthy children (2-5 years old), attending daycare centers was performed. Yogurt containing Lr1505 was administered to children for 6 months (five times a week). Results were statistically compared with those of children from the same community that received a placebo yogurt (without probiotic). Administration of Lr1505 to young children reduced the incidence of infections: 66% of children in the placebo group presented symptoms of infection while only 34% of cases were detected in the Lr1505 group. Significant differences (P<0.05) were detected in the incidence of intestinal infections, upper respiratory tract infections and angina when placebo and Lr1505 groups were compared. Children fed Lr1505 experienced fewer fevers and needed fewer antibiotics than those receiving the placebo. The protective effect of Lr1505 was associated with increased levels of mucosal IgA antibodies. Lr1505 is a promising resource for the development of prevention strategies against mucosal infections that could be effective tools for medical application. This new probiotic strain has been included into official Nutritional Programs in Argentina and it is given to more than 200 thousand children. This project has encouraged local milk production, thanks to the constant demand of probiotic yogurt containing L. rhamnosus CRL1505 by provincial governments, while incorporating innovation to small and medium enterprises.Fil: Villena, Julio Cesar. 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: Nuñez, Martha Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; ArgentinaFil: Corzo, Josefina. Provincia de Tucuman. Sistema Provincial de Salud de Tucuman; ArgentinaFil: Tolaba, René. Universidad Nacional de Tucuman. Facultad de Medicina; Argentina. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hospital del Ni?o Jesus; ArgentinaFil: Faedda, Julio. Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Hospital del Ni?o Jesus; ArgentinaFil: Font, Graciela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentin

Efecto de la leche humana sobre células de sangre y de médula ósea en un modelo de ratos desnutridos: estudio comparativo con leche de vaca

Estudios comparativos entre leche humana y leche de vaca para evaluar su impacto en la recuperación de las células de sangre y de médula ósea afectadas en ratones desnutridos.Comparative studies between human and cow milks in order to evaluate the impact of both milks on the recovery of blood and bone marrow cells affected in malnourished mice.Fil: García, Isabel Mercedes. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina; Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina;Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Zelaya, María Hortensia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Agüero, Graciela. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina

Lactiplantibacillus plantarum as a potential adjuvant and delivery system for the development of sars-cov-2 oral vaccines

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacil-lus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.Fil: Villena, Julio Cesar. Tohoku University; Japón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Li, Chang. Chinese Academy of Sciences; República de ChinaFil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto Superior de Investigaciones Biológicas. Grupo de Investigación y Desarrollo del Noroeste Argentino | Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas. Grupo de Investigación y Desarrollo del Noroeste Argentino; ArgentinaFil: Sacur, Jacinto Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto Superior de Investigaciones Biológicas. Grupo de Investigación y Desarrollo del Noroeste Argentino | Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas. Grupo de Investigación y Desarrollo del Noroeste Argentino; ArgentinaFil: Ren, Linzhu. Jilin University; ChinaFil: Kitazawa, Haruki. Tohoku University; Japó