ArticlePloS one2014
Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Toll-like receptors in corneal ectasia: linking innate immunity to keratoconus.Molecular biology reports · 2026Pooled it
- Oxidative Stress and Redox Imbalance inInternational journal of molecular sciences · 2026Review
- Host Response and Pathogen Load in Acanthamoeba Keratitis: A Histopathological Analysis.Investigative ophthalmology & visual science · 2026Article
- The Immunological Changes in the Skin of BALC/c Mice with Disseminated Acanthamoebiasis.Pathogens (Basel, Switzerland) · 2023Article
- The expression of TLR2 and TLR4 in the kidneys and heart of mice infected with Acanthamoeba spp.Parasites & vectors · 2020Article
- Validation of reference genes for the normalization of RT-qPCR gene expression in Acanthamoeba spp.Scientific reports · 2020Article
- Review
- Expression of Toll-Like Receptors (TLR2 and TLR4) in the Eyes of Mice with Disseminated Acanthamoebiasis.BioMed research international · 2019Article
- Pathobiology and Immunobiology ofThe Yale journal of biology and medicine · 2017Review
- Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6.Infection and immunity · 2017Article
- MyD88 contribution to ocular surface homeostasis.PloS one · 2017Article
- Pattern recognition receptors in microbial keratitis.Eye (London, England) · 2015Review
- Review
- Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury.American journal of translational research · 2015Article
- Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.Investigative ophthalmology & visual science · 2014Article
- Significance of arachidonic acid in ocular infections and inflammation.Inflammation and cell signalingArticle
- Role of protease-activated receptors 2 (PAR2) in ocular infections and inflammation.Receptors & clinical investigationArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Free-living amoebae of the Acanthamoeba species are the causative agent of Acanthamoeba keratitis (AK), a sight-threatening corneal infection that causes severe pain and a characteristic ring-shaped corneal infiltrate. Innate immune responses play an important role in resistance against AK. The aim of this study is to determine if Toll-like receptors (TLRs) on corneal epithelial cells are activated by Acanthamoeba, leading to initiation of inflammatory responses in the cornea. Human corneal epithelial (HCE) cells constitutively expressed TLR1, TLR2, TLR3, TLR4, and TLR9 mRNA, and A. castellanii upregulated TLR4 transcription. Expression of TLR1, TLR2, TLR3, and TLR9 was unchanged when HCE cells were exposed to A. castellanii. IL-8 mRNA expression was upregulated in HCE cells exposed to A. castellanii. A. castellanii and lipopolysaccharide (LPS) induced significant IL-8 production by HCE cells as measured by ELISA. The percentage of total cells positive for TLR4 was higher in A. castellanii stimulated HCE cells compared to unstimulated HCE cells. A. castellanii induced upregulation of IL-8 in TLR4 expressing human embryonic kidney (HEK)-293 cells, but not TLR3 expressing HEK-293 cells. TLR4 neutralizing antibody inhibited A. castellanii-induced IL-8 by HCE and HEK-293 cells. Clinical strains but not soil strains of Acanthamoeba activated TLR4 expression in Chinese hamster corneas in vivo and in vitro. Clinical isolates but not soil isolates of Acanthamoeba induced significant (P< 0.05) CXCL2 production in Chinese hamster corneas 3 and 7 days after infection, which coincided with increased inflammatory cells in the corneas. Results suggest that pathogenic species of Acanthamoeba activate TLR4 and induce production of CXCL2 in the Chinese hamster model of AK. TLR4 may be a potential target in the development of novel treatment strategies in Acanthamoeba and other microbial infections that activate TLR4 in corneal cells.
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