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      Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria

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          Abstract

          Innate immunity is evolutionarily conserved in multicellular organisms and was considered to lack memory until very recently. One of its more characteristic mechanisms is phagocytosis, the ability of cells to engulf, process and eventually destroy any injuring agent. We report the results of an ex vivo experiment in bovine macrophages in which improved clearance of Mycobacterium bovis ( M. bovis) was induced by pre-exposure to a heat killed M. bovis preparation. The effects were independent of humoral and cellular adaptive immune responses and lasted up to six months. Specifically, our results demonstrate the existence of a training effect in the lytic phase of phagocytosis that can be activated by killed mycobacteria, thus suggesting a new mechanism of vaccine protection. These findings are compatible with the recently proposed concept of trained immunity, which was developed to explain the observation that innate immune responses provide unspecific protection against pathogens including other than those that originally triggered the immune response.

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          Most cited references14

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          Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.

          Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans. Copyright © 2014, American Association for the Advancement of Science.
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            Protection against Tuberculosis in Eurasian Wild Boar Vaccinated with Heat-Inactivated Mycobacterium bovis

            Tuberculosis (TB) caused by Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex continues to affect humans and animals worldwide and its control requires vaccination of wildlife reservoir species such as Eurasian wild boar (Sus scrofa). Vaccination efforts for TB control in wildlife have been based primarily on oral live BCG formulations. However, this is the first report of the use of oral inactivated vaccines for controlling TB in wildlife. In this study, four groups of 5 wild boar each were vaccinated with inactivated M. bovis by the oral and intramuscular routes, vaccinated with oral BCG or left unvaccinated as controls. All groups were later challenged with a field strain of M. bovis. The results of the IFN-gamma response, serum antibody levels, M. bovis culture, TB lesion scores, and the expression of C3 and MUT genes were compared between these four groups. The results suggested that vaccination with heat-inactivated M. bovis or BCG protect wild boar from TB. These results also encouraged testing combinations of BCG and inactivated M. bovis to vaccinate wild boar against TB. Vaccine formulations using heat-inactivated M. bovis for TB control in wildlife would have the advantage of being environmentally safe and more stable under field conditions when compared to live BCG vaccines. The antibody response and MUT expression levels can help differentiating between vaccinated and infected wild boar and as correlates of protective response in vaccinated animals. These results suggest that vaccine studies in free-living wild boar are now possible to reveal the full potential of protecting against TB using oral M. bovis inactivated and BCG vaccines.
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              Acute lower respiratory infection among Bacille Calmette-Guérin (BCG)-vaccinated children.

              To determine whether Bacille Calmette-Guerin (BCG) vaccination is linked to the risk of acute lower respiratory infection (ALRI) among children <5 years of age.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 November 2016
                2016
                : 11
                : 11
                : e0165607
                Affiliations
                [1 ]Animal Health Department, NEIKER-Tecnalia, Berreaga, 1, 48160 Derio, Bizkaia, Spain
                [2 ]SaBio, Instituto de Investigación en Recursos Cinegéticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo, 13071, Ciudad Real, Spain
                [3 ]Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, 250 McElroy Hall, Stillwater, OK, 74078, United States of America
                [4 ]Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense, Avenida Puerta de Hierro, 28040, Madrid, Spain
                University of Delhi—South Campus, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: RAJ MAH JMG.

                • Data curation: RAJ MAH JMG.

                • Formal analysis: RAJ MAH.

                • Funding acquisition: RAJ JMG MAH.

                • Investigation: MAH JMG RAJ.

                • Methodology: RAJ MAH JMG NA.

                • Project administration: RAJ JMG MAH.

                • Resources: JMG IAS MAH.

                • Supervision: RAJ.

                • Validation: MAH JMG NA.

                • Visualization: RAJ.

                • Writing – original draft: RAJ MAH.

                • Writing – review & editing: RAJ MAH JMG JDF CG LD.

                [¤]

                Current address: SERIDA, Carretera de Oviedo, 33300 Villaviciosa, Asturias, Spain

                Article
                PONE-D-16-19622
                10.1371/journal.pone.0165607
                5098821
                27820836
                28e48c63-fb41-4cd7-850c-2b8e0e1dec93
                © 2016 Juste et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 May 2016
                : 15 October 2016
                Page count
                Figures: 3, Tables: 1, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100007652, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria;
                Award ID: RTA2011-00049
                Award Recipient :
                Funded by: EU-Seventh Framework Programme
                Award ID: 613799
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003329, Ministerio de Economía y Competitividad;
                Award ID: AGL2014-56305
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000780, European Commission;
                Award ID: FEDER
                Award Recipient :
                Funding for these studies was provided by the EU project WildTBVac (Contract #613799) and by grants from the Instituto Nacional de Investigación y Tencología Agraria y alimentaria (INIA, RTA2011-00049) and the Ministry of Science (MINECO, AGL2014-56305) and European Funds Regional Development (FEDER).
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Immune Response
                Medicine and Health Sciences
                Immunology
                Immune Response
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Phagocytosis
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Macrophages
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                Macrophages
                Biology and Life Sciences
                Immunology
                Immunity
                Humoral Immunity
                Humoral Immune Response
                Medicine and Health Sciences
                Immunology
                Immunity
                Humoral Immunity
                Humoral Immune Response
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Biology and Life Sciences
                Veterinary Science
                Veterinary Medicine
                Livestock Care
                Biology and Life Sciences
                Organisms
                Bacteria
                Actinobacteria
                Mycobacterium Bovis
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Vaccines
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Vaccines
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Vaccines
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