Rhinovirus-Induced Macrophage Cytokine Expression Does Not Require Endocytosis or Replication

Saba, Thomas G.; Chung, Yutein; Hong, Jun Young; Sajjan, Uma S.; Bentley, J. Kelley; Hershenson, Marc B.

doi:10.1165/rcmb.2013-0354oc

Cited by 19 publications

(26 citation statements)

References 44 publications

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“…TLR3 null mice infected with RV1B show normal IFN responses and unchanged viral titers, but reduced lung inflammatory responses and airways responsiveness 6 . On the other hand, RV-induced cytokine expression and viral attachment were abolished in bone marrow-derived macrophages from TLR2 but not TLR3 knockout mice 7 , suggesting a specific requirement of TLR2 in macrophage-mediated responses. TLR2-dependent cytokine expression did not depend on viral endocytosis or replication.…”

Section: Introductionmentioning

confidence: 89%

Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation

Han

Chung

Hong

et al. 2016

Journal of Allergy and Clinical Immunology

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Background We have shown that rhinovirus (RV), a cause of asthma exacerbations, colocalizes with CD68- and CD11b-positive airway macrophages following experimental infection in humans. We have also shown that RV-induced cytokine expression is abolished in TLR2−/− bone marrow-derived macrophages. Objective We hypothesize that TLR2+ macrophages are required and sufficient for RV-induced airway inflammation in vivo. Methods To determine the requirement and sufficiency of TLR2 for RV-induced airway responses, naïve and ovalbumin-sensitized and challenged C57BL/6 wild-type and TLR2−/− mice were infected with RV1B followed by IgG or anti-TLR2. Bone marrow chimera experiments using OVA-treated C57BL/6 and TLR2−/− mice were also performed. Finally, naïve TLR2−/− mice underwent intranasal transfer of bone marrow-derived wild type macrophages. Results RV1B infection of naïve wild-type mice induced an influx of airway neutrophils and CD11b+ exudative macrophages which was reduced in TLR2−/− mice. In allergen-exposed mice, RV-induced neutrophilic and eosinophilic airway inflammation and hyperresponsiveness were reduced in TLR2−/− and anti-TLR2-treated mice. Transfer of TLR2−/− bone marrow into wild type ovalbumin-treated, C57BL/6 mice blocked RV-induced airway responses, whereas transfer of wild type marrow to TLR2−/− mice restored them. Finally, transfer of wild-type macrophages to naïve TLR2−/− mice was sufficient for neutrophilic inflammation after RV infection, whereas macrophages treated with IL-4 (to induce M2 polarization) were sufficient for eosinophilic inflammation, mucous metaplasia and airways hyperresponsiveness. Conclusions TLR2 is required for early inflammatory responses induced by RV, and TLR2+ macrophages are sufficient to confer airway inflammation to TLR2−/− mice, with the pattern of inflammation depending on macrophage activation state.

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Section: Introductionmentioning

confidence: 89%

Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation

Han

Chung

Hong

et al. 2016

Journal of Allergy and Clinical Immunology

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“…The involvement of TLR7 and 8, sensing single-stranded RNA, and TLR2 recognizing viral capsid was also confirmed [128, 129]; however, the role of retinoic acid inducible gene-1 (RIG-I) that binds to the 5' triphosphate motif (which is not exposed but covalently linked to the viral protein g (VPg) in all picornaviruses) is more controversial [130, 131]. RV-induced proinflammatory cytokine response in macrophages was mainly TLR2 dependent in a mouse model and did not require viral endocytosis or replication [132]. …”

Section: Rhinovirus-induced Signaling With Regard To Allergic Diseasementioning

confidence: 99%

Rhinoviruses and Their Receptors: Implications for Allergic Disease

Bochkov

Gern

2016

Curr Allergy Asthma Rep

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Human rhinoviruses (RVs) are picornaviruses that can cause a variety of illnesses including the common cold, lower respiratory tract illnesses such as bronchitis and pneumonia, and exacerbations of asthma. RVs are classified into three species, RV-A, B and C, which include over 160 types. They utilize three major types of cellular membrane glycoproteins to gain entry into the host cell: intercellular adhesion molecule 1 (ICAM-1) (the majority of RV-A and all RV-B), low density lipoprotein receptor (LDLR) family members (12 RV-A types) and cadherin-related family member 3 (CDHR3) (RV-C). CDHR3 is a member of cadherin superfamily of transmembrane proteins with yet unknown biological function, and there is relatively little information available about the mechanisms of RV-C interaction with CDHR3. A coding single nucleotide polymorphism (rs6967330) in CDHR3 could promote RV-C infections and illnesses in infancy, which could in turn adversely affect the developing lung to increase the risk of asthma. Further studies are needed to determine how RV infections contribute to pathogenesis of asthma and to develop the optimal treatment approach to control asthma exacerbations.

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“…However, several studies using UV-irradiated virus, which is incapable of replication, have suggested that binding to the receptor alone elicits similar responses to replication-competent (live) rhinovirus [127][128][129][130][131]. Interestingly, UV-irradiated rhinovirus has been found to be inert in a number of similar studies [132][133][134][135].…”

Section: The Host Response To Virus Infectionmentioning

confidence: 99%

Viral infections and asthma: an inflammatory interface?

et al. 2014

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Asthma is a chronic inflammatory disease of the airways in which the majority of patients respond to treatment with corticosteroids and b 2 -adrenoceptor agonists. Acute exacerbations of asthma substantially contribute to disease morbidity, mortality and healthcare costs, and are not restricted to patients who are not compliant with their treatment regimens. Given that respiratory viral infections are the principal cause of asthma exacerbations, this review article will explore the relationship between viral infections and asthma, and will put forward hypotheses as to why virus-induced exacerbations occur. Potential mechanisms that may explain why current therapeutics do not fully inhibit virus-induced exacerbations, for example, b 2 -adrenergic desensitisation and corticosteroid insensitivity, are explored, as well as which aspects of virus-induced inflammation are likely to be attenuated by current therapy. @ERSpublications Why do virus-induced asthma exacerbations occur? Mechanisms and interventions

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Rhinovirus-Induced Macrophage Cytokine Expression Does Not Require Endocytosis or Replication

Cited by 19 publications

References 44 publications

Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation

Toll-like receptor 2–expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation

Rhinoviruses and Their Receptors: Implications for Allergic Disease

Viral infections and asthma: an inflammatory interface?

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