Innate Immunity of the Sinonasal Cavity

Vandermeer, J; Sha, Qiuying; Lane, Andrew P.; Schleimer, Robert P.

doi:10.1001/archotol.130.12.1374

Cited by 71 publications

(16 citation statements)

References 40 publications

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“…Vandermeer et al [17] demonstrated that mRNAs for TLRs were expressed in the human sinonasal mucosa of CRS and control patients using real-time PCR. Lane et al [18] showed increased levels of TLR-2 expression and a variety of inflammatory genes in the sinonasal mucosa of CRS patients compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps

Zhao

Wang

Liu

et al. 2011

Int Arch Allergy Immunol

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Objective: To identify the regulatory mechanisms of Toll- like receptor (TLR)-associated genes in chronic rhinosinusitis (CRS) with nasal polyps (NP) using gene microarray analyses. Methods: We pooled: (1) NP biopsy specimens from 10 nonatopic CRS patients and (2) healthy mucosal tissue from 10 additional nonatopic healthy patients (controls). These pooled samples were evaluated by gene microarrays that included 125 genes for TLRs and associated signaling elements. To validate gene product expressions, 20 NP and 15 normal nasal turbinate tissues were evaluated for TLR-9 expression by immunohistochemical staining and Western blots using samples from gland cells, epithelial cells, and mononuclear cells cytologically identified by HE staining. Results: In pooled NP samples compared to pooled controls, 4 genes were upregulated (≧2-fold higher expression) and 19 were downregulated (≤0.5-fold lower expression). TLR-9 was an upregulated gene in NP tissue. Compared to control tissue, there were significantly higher percentages of TLR-9 positively stained NP gland cells, epithelial cells, and mononuclear cells (p < 0.001). On Western blots, while both normal and NP tissues expressed TLR-9 protein, the expression was significantly more pronounced for NP tissue (p < 0.001). Conclusions: Inflammation associated with CRS may be due to dysregulated innate immune elements, particularly TLR-9 and its associated signal transduction elements, which may impact upon prolonged activation of adaptive immune responses in the sinonasal mucosa.

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Section: Discussionmentioning

confidence: 99%

Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps

Zhao

Wang

Liu

et al. 2011

Int Arch Allergy Immunol

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“…Toll-like receptors (TLR 1 through TLR10) are expressed in sinonasal epithelium [131, 132]. Signaling through TLRs results in production of cytokines and chemokines along with antimicrobial peptides.…”

Section: Host Factors and The Microbiome In Crsmentioning

confidence: 99%

A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

Mahdavinia

Keshavarzian

Tobin

et al. 2015

Clin Experimental Allergy

125

126

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Chronic rhinosinusitis (CRS) has been known as a disease with strong infectious and inflammatory components for decades. The recent advancement in methods identifying microbes has helped implicate the airway microbiome in inflammatory respiratory diseases such as asthma and COPD. Such studies support a role of resident microbes in both health and disease of host tissue, especially in the case of inflammatory mucosal diseases. Identifying interactive events between microbes and elements of the immune system can help us to uncover the pathogenic mechanisms underlying chronic rhinosinusitis. Here we provide a review of the findings on the complex upper respiratory microbiome in CRS in comparison to healthy controls. Furthermore, we have reviewed the defects and alterations of the host immune system that interact with microbes and could be associated with dysbiosis in CRS.

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“…1-4 Cathelicidins are a family of propeptides consisting of a highly conserved N-terminal sequence (cathelin) and a heterogeneous cationic and antimicrobially active C-terminal domain. 9 They are produced by monocytes and macrophages, but have also been detected in respiratory epithelia and thought to participate in nascent airway protection.…”

Section: Introductionmentioning

confidence: 99%

Assessment of epithelial innate antimicrobial factors in sinus tissue from patients with and without chronic rhinosinusitis

Lee

Escobar

Anouseyan

et al. 2014

Int Forum Allergy Rhinol

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Background Airway secretions contain endogenous antimicrobial factors (AMFs) which contribute to the innate host defense of the respiratory tract. Antibacterial peptides as well as host-derived lipids including cholesteryl esters have been detected in maxillary lavage fluid. Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in cholesteryl ester production. The purpose of this study is to determine if such intrinsic microbicidal molecules are acutely expressed within sinus tissue and to compare levels of expression between patients with and without chronic rhinosinusitis (CRS). Methods Sinus tissue was obtained from subjects with (24) and without (9) a history of CRS. Six CRS patients had nasal polyposis (CRSwNP). Immunofluorescence staining for human neutrophil peptide (HNP) was done as a marker for inflammation. RT-PCR following RNA extraction was used to quantify the expression of SOAT-1, the epithelial beta-defensins (HBD2,3), and the cathelicidin LL37 with ribosomal protein RPLP0 as the housekeeping gene. Results Immunofluorescence showed significant increase in HNP staining in CRS patients without nasal polyposis (CRSsNP) versus non-CRS specimens (p=0.010), in agreement with clinical inflammation status. SOAT1 mRNA expression was also upregulated in CRSsNP compared to non-CRS (p=0.041) and CRSwNP (p=0.005) patients; while increases for HBD2 and HBD3 were less prominent. LL37 was either absent or expressed at very low levels in all samples. Conclusions Increased biosynthesis of SOAT1, a key enzyme for antimicrobial cholesteryl ester production, was observed in the sinus tissue of CRSsNP but not in CRSwNP patients. This further supports the novel concept of lipid-mediated innate mucosal defense and delineates CRS with and without nasal polyposis as distinct subtypes.

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Innate Immunity of the Sinonasal Cavity

Cited by 71 publications

References 40 publications

Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps

Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps

A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

Assessment of epithelial innate antimicrobial factors in sinus tissue from patients with and without chronic rhinosinusitis

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