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      Host-microbial interactions in patients with chronic rhinosinusitis

      research-article
      , MD
      The Journal of Allergy and Clinical Immunology
      American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc.
      Chronic rhinosinusitis, host, microbial, biofilm, innate, immunity, antimicrobial, AFRS, Allergic fungal rhinosinusitis, BPI, Bactericidal/permeability-increasing protein, CD, Crohn disease, Cp110, Centrosomal protein 110, CRS, Chronic rhinosinusitis, CRSsNP, Chronic rhinosinusitis without nasal polyps, CRSwNP, Chronic rhinosinusitis with nasal polyposis, CSLM, Confocal scanning laser microscopy, DMBT1, Deleted in malignant brain tumor 1, EMCRS, Eosinophilic mucin chronic rhinosinusitis, FISH, Fluorescence in situ hybridization, hBD, Human β-defensin, HC, Healthy control subject, IBD, Inflammatory bowel disease, IESA, Intraepithelial Staphylococcus aureus, IL-22R, IL-22 receptor, LBP, LPS-binding protein, MBL, Mannose-binding lectin, NO, Nitric oxide, NOD, Nucleotide-binding oligomerization domain, NP, Nasal polyp, PCD, Primary ciliary dyskinesia, PLUNC, Palate lung and nasal epithelium clone, PNEC, Cultured primary nasal epithelial cell, SEB, Staphylococcal enterotoxin B, SEM, Scanning electron microscopy, SLPI, Secretory leukocyte proteinase inhibitor, SP-A, Surfactant protein A, SP-D, Surfactant protein D, TEM, Transmission electron microscopy, TLR, Toll-like receptor

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          Abstract

          There has been considerable investigation of host-microbial interactions in patients with chronic rhinosinusitis (CRS) in hopes of elucidating mechanisms of disease and better treatment. Most attention has been paid to bacterial infection and potential underlying defects in innate immunity. Bacterial biofilm is present in most patients with CRS undergoing surgical intervention, and its presence is associated with more severe disease and worse surgical outcomes. A role for viral or fungal infection in patients with CRS is less clear. There is no evidence for a primary defect in mucociliary clearance in most patients with CRS. Decreased levels of certain antimicrobial proteins, most notably lactoferrin, have been found in sinus secretions, whereas levels of other antimicrobial proteins have been found to be normal. No primary defects in Toll-like receptors have been found in patients with CRS, although a 50% reduced expression of Toll-like receptor 9 was reported in patients with recalcitrant nasal polyps. A polymorphism in a bitter taste receptor was recently associated with refractory CRS and persistent Pseudomonas aeruginosa infection. A downregulation of innate immunity by maladaptive T H2 tissue inflammation has also been described in patients with recalcitrant nasal polyps, suggesting a link to persistent infection. To date, an effective means of restoring host-microbial balance and mitigating disease in patients with CRS remains elusive.

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          Most cited references173

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          Recognition of microorganisms and activation of the immune response.

          The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
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            Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.

            Nod2 activates the NF-kappaB pathway following intracellular stimulation by bacterial products. Recently, mutations in Nod2 have been shown to be associated with Crohn's disease, suggesting a role for bacteria-host interactions in the etiology of this disorder. We show here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptidoglycan motif common to all bacteria. Moreover, the 3020insC frameshift mutation, the most frequent Nod2 variant associated with Crohn's disease patients, fully abrogates Nod2-dependent detection of peptidoglycan and MDP. Together, these results impact on the understanding of Crohn's disease development. Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound.
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              Role of deficient type III interferon-lambda production in asthma exacerbations.

              Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.
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                Author and article information

                Contributors
                Journal
                J Allergy Clin Immunol
                J. Allergy Clin. Immunol
                The Journal of Allergy and Clinical Immunology
                American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc.
                0091-6749
                1097-6825
                28 November 2013
                March 2014
                28 November 2013
                : 133
                : 3
                : 640-653.e4
                Affiliations
                [1]Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Boston, Mass
                Author notes
                []Corresponding author: Daniel L. Hamilos, MD, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, 55 Fruit St, Bulfinch-422, Boston, MA 02114. dhamilos@ 123456partners.org
                Article
                S0091-6749(13)01483-8
                10.1016/j.jaci.2013.06.049
                7112254
                24290275
                9b74f6c9-0954-40c1-a509-dd139623b9ef
                Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 14 January 2013
                : 25 June 2013
                : 27 June 2013
                Categories
                Article

                Immunology
                chronic rhinosinusitis,host,microbial,biofilm,innate,immunity,antimicrobial,afrs, allergic fungal rhinosinusitis,bpi, bactericidal/permeability-increasing protein,cd, crohn disease,cp110, centrosomal protein 110,crs, chronic rhinosinusitis,crssnp, chronic rhinosinusitis without nasal polyps,crswnp, chronic rhinosinusitis with nasal polyposis,cslm, confocal scanning laser microscopy,dmbt1, deleted in malignant brain tumor 1,emcrs, eosinophilic mucin chronic rhinosinusitis,fish, fluorescence in situ hybridization,hbd, human β-defensin,hc, healthy control subject,ibd, inflammatory bowel disease,iesa, intraepithelial staphylococcus aureus,il-22r, il-22 receptor,lbp, lps-binding protein,mbl, mannose-binding lectin,no, nitric oxide,nod, nucleotide-binding oligomerization domain,np, nasal polyp,pcd, primary ciliary dyskinesia,plunc, palate lung and nasal epithelium clone,pnec, cultured primary nasal epithelial cell,seb, staphylococcal enterotoxin b,sem, scanning electron microscopy,slpi, secretory leukocyte proteinase inhibitor,sp-a, surfactant protein a,sp-d, surfactant protein d,tem, transmission electron microscopy,tlr, toll-like receptor

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