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Pathogenic Strains of Acanthamoeba Are Recognized by TLR4 and Initiated Inflammatory Responses in the Cornea

Overview of attention for article published in PLOS ONE, March 2014
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Title
Pathogenic Strains of Acanthamoeba Are Recognized by TLR4 and Initiated Inflammatory Responses in the Cornea
Published in
PLOS ONE, March 2014
DOI 10.1371/journal.pone.0092375
Pubmed ID
Authors

Hassan Alizadeh, Trivendra Tripathi, Mahshid Abdi, Ashley Dawn Smith

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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 3%
Unknown 34 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 23%
Student > Ph. D. Student 7 20%
Student > Bachelor 6 17%
Researcher 5 14%
Other 2 6%
Other 2 6%
Unknown 5 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 29%
Medicine and Dentistry 7 20%
Immunology and Microbiology 4 11%
Biochemistry, Genetics and Molecular Biology 3 9%
Environmental Science 1 3%
Other 3 9%
Unknown 7 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 November 2014.
All research outputs
#20,243,777
of 22,771,140 outputs
Outputs from PLOS ONE
#173,375
of 194,253 outputs
Outputs of similar age
#189,678
of 221,027 outputs
Outputs of similar age from PLOS ONE
#4,944
of 5,679 outputs
Altmetric has tracked 22,771,140 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194,253 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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