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      Research progress on Toll-like receptor signal transduction and its roles in antimicrobial immune responses

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          Abstract

          When microorganisms invade a host, the innate immune system first recognizes the pathogen-associated molecular patterns of these microorganisms through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are known transmembrane PRRs existing in both invertebrates and vertebrates. Upon ligand recognition, TLRs initiate a cascade of signaling events; promote the pro-inflammatory cytokine, type I interferon, and chemokine expression; and play an essential role in the modulation of the host’s innate and adaptive immunity. Therefore, it is of great significance to improve our understanding of antimicrobial immune responses by studying the role of TLRs and their signal molecules in the host’s defense against invading microbes. This paper aims to summarize the specificity of TLRs in recognition of conserved microbial components, such as lipoprotein, lipopolysaccharide, flagella, endosomal nucleic acids, and other bioactive metabolites derived from microbes. This set of interactions helps to elucidate the immunomodulatory effect of TLRs and the signal transduction changes involved in the infectious process and provide a novel therapeutic strategy to combat microbial infections.

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          Most cited references136

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          Pattern recognition receptors and inflammation.

          Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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            Pathogen recognition and innate immunity.

            Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
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              The nuclear factor NF-kappaB pathway in inflammation.

              The nuclear factor NF-kappaB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-kappaB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-kappaB has long been considered the "holy grail" as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-kappaB in inflammation in light of these recent studies.
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                Author and article information

                Contributors
                ppxia@yzu.edu.cn
                mx120190734@yzu.edu.cn
                1435946956@qq.com
                yanli3559@163.com
                mengxia_1@126.com
                dqd@yzu.edu.cn
                yzgqzhu@yzu.edu.cn
                Journal
                Appl Microbiol Biotechnol
                Appl Microbiol Biotechnol
                Applied Microbiology and Biotechnology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0175-7598
                1432-0614
                28 June 2021
                : 1-15
                Affiliations
                [1 ]GRID grid.268415.c, College of Veterinary Medicine (Institute of Comparative Medicine), , Yangzhou University, ; 12th East Wenhui Road, Yangzhou, 225009 China
                [2 ]GRID grid.268415.c, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, ; Yangzhou, 225009 China
                [3 ]GRID grid.268415.c, Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, , Yangzhou University, ; Yangzhou, 225009 China
                Author information
                http://orcid.org/0000-0002-3693-1312
                Article
                11406
                10.1007/s00253-021-11406-8
                8236385
                34180006
                094fdb59-5f74-4531-b4be-112090419567
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 25 February 2021
                : 7 May 2021
                : 8 June 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 32072820, 31702242
                Categories
                Mini-Review

                Biotechnology
                toll-like receptors,microorganism,anti-infective immunity,signal transduction
                Biotechnology
                toll-like receptors, microorganism, anti-infective immunity, signal transduction

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