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

Study on Probiotic Lactic Acid Bacteria and Their Applications to New Functional Foods

In the present mini review, we describe 1) a new screening system for selecting probiotic strains from lactic acid bacteria (LAB), mainly Lactobacillus acidophilus group bacteria, with strong adhesion to the human intestinal tract, 2) characteristics of immunostimulative oligo DNA motifs in LAB (L. gasseri) strains and a new evaluation system with a transfectant expressing porcine Toll-1ike receptor 9 for selection of immunostimulative LABs, and 3) characteristics of antimicrobial peptides (bacteriocins), especially gasericin A from L. gasseri LA39. In the future, it is expected that superior functional foods containing more effective probiotic LAB will be developed by the use of our proposed mass screening system

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

Swine Intestinal Immunity via Toll-like Receptors and Its Advanced Application to Food Immunology

Recent interest has focused on the importance of intestinal immunity for the host defense, but to date, not much has been known about the underlying mechanisms. Toll-like receptor (TLR) family plays an important role in the defense through recognizing bacterial pathogen associated molecular patterns (PAMPs). Our research on the bioregulatory function of food products has investigated the immunoregulatory effects of lactic acid bacteria (LAB) via TLRs. Studies in swine, which is expected as a human model, have been examined intestinal immunoregulation by the LAB. Our research has now demonstrated modulation of intestinal immunity mediated by TLRs in Peyer\u27s patches and the mesenteric lymph nodes. On the basis of our study, efforts have also been made to develop an immunoassay system for immunobiotic LAB DNA and cell wall components to evaluate immunoregulation by the LAB via TLRs. The findings in our research activities may provide important clues at the molecular level on TLR signal transduction pathways and recognition mechanisms. They also provide impetus to further delineate the activation mechanism of the innate immune response. In addition, identification of biofactors from LAB with immunoactivity, and better understanding of cytokine induction and intestinal immune regulation hold promise in basic research and development of "immunobiotic foods" to prevent specific diseases

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

CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9

We previously reported the strong immunostimulatory effects of a CpG oligodeoxynucleotide (ODN), designated MsST, from the lacZ gene of Streptococcus (S.) thermophilus ATCC19258. Here we show that 24 h of stimulation with MsST in mouse splenocytes and peritoneal macrophages strongly induces expression of interleukin (IL)-33, a cytokine in the IL-1 superfamily. Other IL-1 superfamily members, including IL-1 alpha, IL-1 beta and IL-18, are down-regulated after 24 h of stimulation of MsST. We also found that MsST-induced IL-33 mRNA expression is inhibited by the suppressive ODN A151, which can inhibit Toll-like receptor 9 (TLR9)-mediated responses. This is the first report to show that IL-33 can be induced by CpG ODNs. The strong induction of IL-33 by MsST suggests that it may be a potential therapeutic ODN for the treatment of inflammatory disease. The presence of a strong CpG ODN in S. thermophilus also suggests that the bacterium may be a good candidate as a starter culture for the development of new physiologically functional foods.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 394(1):81-86 (2010)journal articl

Identification of a potent immunostimulatory oligodeoxynucleotide from Streptococcus thermophilus lacZ

Immunostimulatory sequences of oligodeoxynucleotides (ODNs), such as CpG ODNs, are potent stimulators of innate immunity. Here, we identified a strong immunostimulatory CpG ODN, which we named MsST, from the lac Z gene of Streptococcus (S.) thermophilus ATCC19258, and we evaluated its immune functions. In in vitro studies, MsST had a similar ability as the murine prototype CpG ODN 1555 to induce inflammatory cytokine production and cell proliferation. In mouse splenocytes, MsST increased the number of CD80+CD11c+and CD86+CD11c+ dendritic cells and CD4+CD25+ regulatory T cells. We also analyzed the effects of MsST on the expression of regulatory cytokines by real-time quantitative PCR. MsST was more potent at inducing interleukin-10 expression than the ODN control 1612, indicating that MsST can augment the regulatory T cell response via Toll-like receptor 9, which plays an important role in suppressing T helper type 2 responses. These results suggest that S. thermophilus, whose genes include a strong Immunostimulatory sequence-ODN, is a good candidate for a starter culture to develop new physiologically functional foods and feeds.ArticleANIMAL SCIENCE JOURNAL. 80(5):597-604 (2009)journal articl