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      Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

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          Abstract

          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.

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          Most cited references62

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          Microbiota regulates immune defense against respiratory tract influenza A virus infection.

          Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1β and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.
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            Probiotic Mechanisms of Action

            Probiotics are live microorganisms that provide health benefits to the host when ingested in adequate amounts. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects have not been fully elucidated yet. Several important mechanisms underlying the antagonistic effects of probiotics on various microorganisms include the following: modification of the gut microbiota, competitive adherence to the mucosa and epithelium, strengthening of the gut epithelial barrier and modulation of the immune system to convey an advantage to the host. Accumulating evidence demonstrates that probiotics communicate with the host by pattern recognition receptors, such as toll-like receptors and nucleotide-binding oligomerization domain-containing protein-like receptors, which modulate key signaling pathways, such as nuclear factor-ĸB and mitogen-activated protein kinase, to enhance or suppress activation and influence downstream pathways. This recognition is crucial for eliciting measured antimicrobial responses with minimal inflammatory tissue damage. A clear understanding of these mechanisms will allow for appropriate probiotic strain selection for specific applications and may uncover novel probiotic functions. The goal of this systematic review was to explore probiotic modes of action focusing on how gut microbes influence the host.
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              Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens.

              How can probiotic bacteria transduce their health benefits to the host? Bacterial cell surface macromolecules are key factors in this beneficial microorganism-host crosstalk, as they can interact with host pattern recognition receptors (PRRs) of the gastrointestinal mucosa. In this Review, we highlight the documented signalling interactions of the surface molecules of probiotic bacteria (such as long surface appendages, polysaccharides and lipoteichoic acids) with PRRs. Research on host-probiotic interactions can benefit from well-documented host-microorganism studies that span the spectrum from pathogenicity to mutualism. Distinctions and parallels are therefore drawn with the interactions of similar molecules that are presented by gastrointestinal commensals and pathogens.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 December 2016
                2016
                : 7
                : 633
                Affiliations
                [1] 1Immunobiotics Research Group , Tucuman, Argentina
                [2] 2Institute of Applied Biochemistry, National University of Tucuman , Tucuman, Argentina
                [3] 3Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET) , Tucuman, Argentina
                [4] 4Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University , Sendai, Japan
                [5] 5Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University , Sendai, Japan
                Author notes

                Edited by: José Roberto Mineo, Federal University of Uberlandia, Brazil

                Reviewed by: Mirko Trilling, University of Duisburg, Germany; Dina Weilhammer, Lawrence Livermore National Laboratory (DOE), USA

                *Correspondence: Haruki Kitazawa, haruki.kitazawa.c7@ 123456tohoku.ac.jp ; Julio Villena, jcvillena@ 123456cerela.org.ar

                Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2016.00633
                5179578
                28066442
                4b906851-9652-489d-bf0b-aa052a69743a
                Copyright © 2016 Zelaya, Alvarez, Kitazawa and Villena.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 September 2016
                : 12 December 2016
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 94, Pages: 16, Words: 11690
                Funding
                Funded by: Japan Society for the Promotion of Science 10.13039/501100001691
                Award ID: No. 16H05019, No. 16K15028, Open Partnership Joint Projects of JSPS Bilateral Joint Research Projects
                Funded by: Agencia Nacional de Promoción Científica y Tecnológica 10.13039/501100003074
                Award ID: PICT-2013 3219
                Categories
                Immunology
                Review

                Immunology
                immunobiotics,influenza virus,inflammation,coagulation,respiratory immunity
                Immunology
                immunobiotics, influenza virus, inflammation, coagulation, respiratory immunity

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