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      Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

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          Abstract

          Respiratory syncytial virus (RSV) is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection.

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          Most cited references125

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          Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

          MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
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            Preparing for the first breath: genetic and cellular mechanisms in lung development.

            The mammalian respiratory system--the trachea and the lungs--arises from the anterior foregut through a sequence of morphogenetic events involving reciprocal endodermal-mesodermal interactions. The lung itself consists of two highly branched, tree-like systems--the airways and the vasculature--that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as branching morphogenesis, vascular development, and the differentiation of multipotent progenitor populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding respiratory disorders, congenital defects in human neonates, and how the disruption of morphogenetic programs early in lung development can lead to deficiencies that persist throughout life. (c) 2010 Elsevier Inc. All rights reserved.
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              Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero.

              As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/509822
                URI : http://frontiersin.org/people/u/24431
                URI : http://frontiersin.org/people/u/439448
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                19 February 2018
                2018
                : 9
                : 226
                Affiliations
                [1] 1Department of Pathology, University of Michigan , Ann Arbor, MI, United States
                [2] 2University of Michigan, Mary H. Weiser Food Allergy Center , Ann Arbor, MI, United States
                Author notes

                Edited by: Steven Varga, University of Iowa, United States

                Reviewed by: Rita Carsetti, Bambino Gesù Ospedale Pediatrico (IRCCS), Italy; Jason Kyle Whitmire, University of North Carolina at Chapel Hill, United States

                *Correspondence: Catherine Ptaschinski, cptaschi@ 123456med.umich.edu

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

                Article
                10.3389/fimmu.2018.00226
                5825926
                29515570
                ab3739b0-7143-4621-9b79-2ced8dc695e4
                Copyright © 2018 Fonseca, Lukacs and Ptaschinski.

                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) and the copyright owner 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
                : 15 November 2017
                : 26 January 2018
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 165, Pages: 15, Words: 13970
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01-AI036302
                Funded by: American Lung Association 10.13039/100002590
                Award ID: Biomedical Research Grant
                Categories
                Immunology
                Review

                Immunology
                respiratory syncytial virus,neonatal immunity,epigenetics,microbiome,metabolites
                Immunology
                respiratory syncytial virus, neonatal immunity, epigenetics, microbiome, metabolites

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