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      Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt

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          Abstract

          The host-pathogen interface is a crucial battleground during bacterial infection in which host defenses are met with an array of bacterial counter-mechanisms whereby the invader aims to make the host environment more favorable to survival and dissemination. Interestingly, the eukaryotic Wnt signaling pathway has emerged as a key player in the host and pathogen tug-of-war. Although studied for decades as a regulator of embryogenesis, stem cell maintenance, bone formation, and organogenesis, Wnt signaling has recently been shown to control processes related to bacterial infection in the human host. Wnt signaling pathways contribute to cell cycle control, cytoskeleton reorganization during phagocytosis and cell migration, autophagy, apoptosis, and a number of inflammation-related events. Unsurprisingly, bacterial pathogens have evolved strategies to manipulate these Wnt-associated processes in order to enhance infection and survival within the human host. In this review, we examine the different ways human bacterial pathogens with distinct host cell tropisms and lifestyles exploit Wnt signaling for infection and address the potential of harnessing Wnt-related mechanisms to combat infectious disease.

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          Most cited references134

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          Autophagy defends cells against invading group A Streptococcus.

          We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells. After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes. In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens.
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            Dishevelled: The hub of Wnt signaling.

            Wnt signaling controls a variety of developmental and homeostatic events. As a key component of Wnt signaling, Dishevelled (Dvl/Dsh) protein relays Wnt signals from receptors to downstream effectors. In the canonical Wnt pathway that depends on the nuclear translocation of beta-catenin, Dvl is recruited by the receptor Frizzled and prevents the constitutive destruction of cytosolic beta-catenin. In the non-canonical Wnt pathways such as Wnt-Frizzled/PCP (planar cell polarity) signaling, Dvl signals via the Daam1-RhoA axis and the Rac1 axis. In addition, Dvl plays important roles in Wnt-GSK3beta-microtubule signaling, Wnt-calcium signaling, Wnt-RYK signaling, Wnt-atypical PKC signaling, etc. Dvl also functions to mediate receptor endocytosis. To fulfill its multifaceted functions, it is not surprising that Dvl associates with various kinds of proteins. Its activity is also modulated dynamically by phosphorylation, ubiquitination and degradation. In this review, we summarize the current understanding of Dvl functions in Wnt signal transduction and its biological functions in mouse development, and also discuss the molecular mechanisms of its actions. 2009 Elsevier Inc. All rights reserved.
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              Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994.

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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
                17 October 2019
                2019
                : 10
                : 2390
                Affiliations
                [1] 1Department of Pathology, University of Texas Medical Branch , Galveston, TX, United States
                [2] 2Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX, United States
                [3] 3Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch , Galveston, TX, United States
                [4] 4Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX, United States
                Author notes

                Edited by: Wanderley De Souza, Federal University of Rio de Janeiro, Brazil

                Reviewed by: Emile Santos Barrias, National Institute of Metrology, Quality and Technology, Brazil; Arshad Khan, McGovern Medical School, University of Texas, United States

                *Correspondence: Jere W. McBride jemcbrid@ 123456utmb.edu

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

                Article
                10.3389/fimmu.2019.02390
                6811524
                31681283
                f617c342-6a36-47ac-8c3e-77d036bd534c
                Copyright © 2019 Rogan, Patterson, Wang and McBride.

                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(s) 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
                : 01 July 2019
                : 23 September 2019
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 166, Pages: 22, Words: 16442
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases 10.13039/100000060
                Award ID: AI106859
                Award ID: AI123610
                Award ID: AI126144
                Categories
                Immunology
                Review

                Immunology
                wnt,β-catenin,bacteria,pathogen,innate immunity,immunoevasion
                Immunology
                wnt, β-catenin, bacteria, pathogen, innate immunity, immunoevasion

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