Conjunctival transcriptome analysis reveals the overexpression of multiple pattern recognition receptors in vernal keratoconjunctivitis

Leonardi, Andrea; Daull, Philippe; Garrigue, Jean-Sébastien; Cavarzeran, Fabiano; Docquier, Mylène; Stefano, Antonino Di; Tarricone, Elena; Brun, Paola

doi:10.1016/j.jtos.2020.09.009

Cited by 25 publications

(25 citation statements)

References 55 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Toll-like receptors (TLRs) are a family of PRRs capable of recognizing various PAMPs, leading to a signaling cascade and secretion of a variety of interferons, cytokines, and chemokines [ 55 ]. The human conjunctiva has been shown to express various TLRs to provide ocular surface immunity against invading pathogens [ 56 , 57 ]. In our prior study with Zika virus infection of corneal epithelial cells, we found induction of TLR3 leading to antiviral innate immune response [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

et al. 2022

View full text Add to dashboard Cite

Purpose SARS-CoV-2 RNA has been detected in ocular tissues, but their susceptibility to SARS-CoV-2 infection is unclear. Here, we tested whether SARS-CoV-2 can infect human conjunctival epithelial cells (hCECs) and induce innate immune response. Methods Conjunctival tissue from COVID-19 donors was used to detect SARS-CoV-2 spike and envelope proteins. Primary hCECs isolated from cadaver eyes were infected with the parental SARS-CoV-2 and its beta variant of concern (VOC). Viral genome copy number, expression of viral entry receptors, TLRs, interferons, innate immune response genes was determined by qPCR. Viral receptors were examined in hCECs and tissue sections by immunostaining. Spike protein was detected in the cell culture supernatant by dot blot. Results Spike and envelope proteins were found in conjunctiva from COVID-19 patients. SARS-CoV-2 infected hCECs showed high viral copy numbers at 24–72h post-infection; spike protein levels were the highest at 24hpi. Viral entry receptors ACE2, TMPRSS2, CD147, Axl, and NRP1 were detected in conjunctival tissue and hCECs. SARS-CoV-2 infection-induced receptor expression at early time points post-infection, but gene expression of most TLRs peaked at 48 or 72hpi. SARS-CoV-2 infected hCECs showed higher expression of genes regulating antiviral response, RIG-I , interferons (α, β, & λ), ISG15 & OAS2 , cytokines ( IL-6, IL1β, TNFα ), and chemokines ( CXCL10, CCL5 ). Compared to the parental strain, beta VOC induced increased viral copy number and innate response in hCECs. Conclusions Conjunctival epithelial cells are susceptible to SARS-CoV-2 infection. Beta VOC is more infectious than the parental strain and evokes a higher antiviral and inflammatory response.

show abstract

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

et al. 2022

View full text Add to dashboard Cite

show abstract

“…A subsequent study also reported that patients with VKC showed improvement in the signs and symptoms after 4 weeks of treatment with Lactobacillus acidophilus eye drops, in association with downregulation of both ICAM-1 and TLR4 [ 70 ]. Recently, conjunctival gene overexpression of pattern recognition receptors (PRRs) in VKC patients was described, including chemokines, proinflammatory cytokines, and TLR4 and TLR8, suggesting a role of host–pathogen interaction in VKC [ 71 ].…”

Section: Role Of Innate Immunity In Vkcmentioning

confidence: 99%

Understanding Vernal Keratoconjunctivitis: Beyond Allergic Mechanisms

Sacchetti

Plateroti

Giustolisi

et al. 2021

Life

View full text Add to dashboard Cite

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of life. The pathogenesis of VKC has not yet been completely understood, and it is still controversial. In fact, VKC is considered an ocular allergic disease due to the involvement of immunoglobulin E, eosinophils, and mast cells, and of a lymphocyte T-helper type 2 reaction. However, approximately half of VKC patients have negative allergological history and testing, suggesting that other pathogenic mechanisms participate in VKC development and severity. Specifically, evidence suggests that genetic, endocrine, neuronal factors and an imbalance of innate immunity are involved in the pathogenesis of VKC. The purpose of this review is to summarize evidence on the pathogenic role of innate immunity, neuroimmune reaction, and hormonal changes in VKC. Increasing understanding of the pathogenic mechanisms behind VKC may lead to the identification of novel biomarkers for diagnosis and/or potential therapeutic targets in order to improve the management of this challenging condition.

show abstract

“…89 The role of altered gut microbiota in the development of uveitis 90 and dry eye 91 has been also established. Interestingly, the multiple 54 Recently, bacterial and fungal dysbiosis has been described in VKC, suggesting that altered conjunctival microbiota composition might be involved in the disease pathogenesis. 92 In VKC, Bacteroidetes and Fusobacteria constitute the core bacterial microbiome, which includes different species of gram-negative bacteria, whereas the fungal microbiome analysis revealed increased abundance of Malasseziaceae family members.…”

Section: Early-life Events Microbiome and Epithelial Barrier Disruptionmentioning

confidence: 99%

Epithelial barrier dysfunction in ocular allergy

Singh

Diebold

Sahu

et al. 2021

Allergy

Self Cite

View full text Add to dashboard Cite

The epithelial barrier is the first line of defense that forms a protective barrier against pathogens, pollutants, and allergens. Epithelial barrier dysfunction has been recently implicated in the development of allergic diseases such as asthma, atopic dermatitis, food allergy, and rhinitis. However, there is limited knowledge on epithelial barrier dysfunction in ocular allergy (OA). Since the ocular surface is directly exposed to the environment, it is important to understand the role of ocular epithelia and their dysfunction in OA. Impaired epithelial barrier enhances allergen uptake, which lead to activation of immune responses and development of chronic inflammation as seen in allergies. Abnormal expression of tight junction proteins that helps to maintain epithelial integrity has been reported in OA but sufficient data not available in chronic atopic (AKC) and vernal keratoconjunctivitis (VKC), the pathophysiology of which is not just complex, but also the current treatments are not completely effective. This review provides an overview of studies, which indicates the role of barrier dysfunction in OA, and highlights how ocular barrier dysfunction possibly contributes to the disease pathogenesis. The review also explores the potential of ocular epithelial barrier repair strategies as preventive and therapeutic approach.

show abstract

Conjunctival transcriptome analysis reveals the overexpression of multiple pattern recognition receptors in vernal keratoconjunctivitis

Cited by 25 publications

References 55 publications

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

SARS-CoV-2 and its beta variant of concern infect human conjunctival epithelial cells and induce differential antiviral innate immune response

Understanding Vernal Keratoconjunctivitis: Beyond Allergic Mechanisms

Epithelial barrier dysfunction in ocular allergy

Contact Info

Product

Resources

About