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      Unraveling the Differences between Gram-Positive and Gram-Negative Probiotics in Modulating Protective Immunity to Enteric Infections

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          Abstract

          The role of intestinal microbiota and probiotics in prevention and treatment of infectious diseases, including diarrheal diseases in children and animal models, is increasingly recognized. Intestinal commensals play a major role in development of the immune system in neonates and in shaping host immune responses to pathogens. Lactobacilli spp. and Escherichia coli Nissle 1917 are two probiotics that are commonly used in children to treat various medical conditions including human rotavirus diarrhea and inflammatory bowel disease. Although the health benefits of probiotics have been confirmed, the specific effects of these established Gram-positive (G+) and Gram-negative (G−) probiotics in modulating immunity against pathogens and disease are largely undefined. In this review, we discuss the differences between G+ and G− probiotics/commensals in modulating the dynamics of selected infectious diseases and host immunity. These probiotics modulate the pathogenesis of infectious diseases and protective immunity against pathogens in a species- and strain-specific manner. Collectively, it appears that the selected G− probiotic is more effective than the various tested G+ probiotics in enhancing protective immunity against rotavirus in the gnotobiotic piglet model.

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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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            Interactions between commensal intestinal bacteria and the immune system.

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              Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota.

              Mononuclear phagocytes are an important component of an innate immune system perceived as a system ready to react upon encounter of pathogens. Here, we show that in response to microbial stimulation, mononuclear phagocytes residing in nonmucosal lymphoid organs of germ-free mice failed to induce expression of a set of inflammatory response genes, including those encoding the various type I interferons (IFN-I). Consequently, NK cell priming and antiviral immunity were severely compromised. Whereas pattern recognition receptor signaling and nuclear translocation of the transcription factors NF-κB and IRF3 were normal in mononuclear phagocytes of germ-free mice, binding to their respective cytokine promoters was impaired, which correlated with the absence of activating histone marks. Our data reveal a previously unrecognized role for postnatally colonizing microbiota in the introduction of chromatin level changes in the mononuclear phagocyte system, thereby poising expression of central inflammatory genes to initiate a powerful systemic immune response during viral infection. Copyright © 2012 Elsevier Inc. All rights reserved.
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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
                27 March 2017
                2017
                : 8
                : 334
                Affiliations
                [1] 1Food Animal Health Research Program (FAHRP), Veterinary Preventive Medicine Department, The Ohio Agricultural Research and Development Center, The Ohio State University , Wooster, OH, USA
                Author notes

                Edited by: Julio Villena, Reference Centre for Lactobacilli (CERELA-CONICET), Argentina

                Reviewed by: Haruki Kitazawa, Tohoku University, Japan; Maria Guadalupe Vizoso Pinto, National University of Tucumán, Argentina

                *Correspondence: Linda J. Saif, saif.2@ 123456osu.edu

                Present address: Kuldeep S. Chattha, Canadian Food Inspection Agency, Lethbridge, AB, Canada; Lulu Shao, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, PA, USA; Anand Kumar, Genomics and Systems Biology, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA

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

                Article
                10.3389/fimmu.2017.00334
                5366325
                28396664
                893c43cf-48d9-4cd5-950e-f03e5a808560
                Copyright © 2017 Kandasamy, Vlasova, Fischer, Chattha, Shao, Kumar, Langel, Rauf, Huang, Rajashekara and Saif.

                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
                : 29 November 2016
                : 08 March 2017
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 79, Pages: 8, Words: 6189
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Award ID: A1099451
                Categories
                Immunology
                Review

                Immunology
                rotavirus,probiotics,escherichia coli nissle,lactobacillus,immunity,children,diarrhea,gnotobiotic piglet disease model

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