Toll-like receptors in ocular surface diseases: overview and new findings

Lambìase, Alessandro; Micera, Alessandra; Mantelli, Flavio; Bombardieri, Stefano

doi:10.1042/cs20100425

Cited by 51 publications

(41 citation statements)

References 84 publications

(115 reference statements)

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“…Studies have demonstrated that Acanthamoeba trophozoites can activate TLR4 expressed on corneal epithelial cells, inducing proinflammatory cytokines and chemokines at the ocular surface (10,32). The activation of TLRs at the ocular surface by Acanthamoeba and the release of cytokines and chemokines can be the triggering events for the recruitment of innate immune cells, such as macrophages and neutrophils (33).…”

Section: Discussionmentioning

confidence: 99%

Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6

et al. 2017

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Acanthamoeba castellanii is a ubiquitous free-living amoeba with a worldwide distribution that can occasionally infect humans, causing particularly severe infections in immunocompromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease, despite the high exposure rates. While macrophages are acknowledged as playing a significant role in Acanthamoeba infections, little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigated the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow-derived macrophages were cocultured with trophozoites of either the laboratory Neff strain or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a proinflammatory macrophage phenotype characterized by the significant production of interleukin-12 (IL-12) and IL-6. However, macrophages cocultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 than the Neff strain. The utilization of macrophages derived from MyD88-, TRIF-, Toll-like receptor 2 (TLR2)-, TLR4-, and TLR2/4-deficient mice indicated that Acanthamoeba-induced proinflammatory cytokine production was through MyD88-dependent, TRIF-independent, TLR4-induced events. This study shows for the first time the involvement of TLRs expressed on macrophages in the recognition of and response to Acanthamoeba trophozoites. KEYWORDS Acanthamoeba, macrophagesA canthamoeba castellanii is a ubiquitous free-living amoeba that has been isolated from both outdoor and indoor environments. It exists as actively feeding, dividing trophozoites and the dormant environmentally resistant cyst. Despite its ability to proliferate and survive as a free-living organism, Acanthamoeba is also a facultative parasite of humans, most frequently causing a painful, potentially blinding infection of the eye, called Acanthamoeba keratitis (AK), in immunocompetent individuals. Acanthamoeba is also an opportunistic parasite, and in immunocompromised individuals it is responsible for an often fatal infection of the brain, named granulomatous amoebic encephalitis (GAE) (1). The ability of the vast majority of immunocompetent humans to resist infection coupled with the susceptibility of the immunocompromised demonstrates the importance of the immune system in resistance to infection. However, and

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Section: Discussionmentioning

confidence: 99%

Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6

et al. 2017

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“…The cornea is the major refractive element of the adult eye, and consists of three layers, including a thick middle layer known as the stroma, separated by basement membranes from an external stratified epithelium and an inner layer of endothelial cells. The corneal epithelium is the interface with the environment and represents an active barrier against pathogens, commensal bacteria, toxic stimuli, and allergens (Lambiase et al, 2011). Due to the constant physical disruption of blinking and tear flow, in addition to the presence of antibacterial components, the ocular surface of healthy individuals inherently supports a small population of bacteria (Graham et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

García

Merayo‐Lloves

Rodrı́guez

et al. 2016

Front. Cell. Infect. Microbiol.

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The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies.

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“…TLRs are expressed in ocular surface, retinal, iris, and corneal epithelial cells [26]–[28]. In the context of intraocular infections, TLRs have been found to be important in inflammation in S. aureus [29] and B. cereus [30] endophthalmitis.…”

Section: Introductionmentioning

confidence: 99%

Role of TLR5 and Flagella in Bacillus Intraocular Infection

2014

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B. cereus possesses flagella which allow the organism to migrate within the eye during a blinding form of intraocular infection called endophthalmitis. Because flagella is a ligand for Toll-like receptor 5 (TLR5), we hypothesized that TLR5 contributed to endophthalmitis pathogenesis. Endophthalmitis was induced in C57BL/6J and TLR5−/− mice by injecting 100 CFU of B. cereus into the mid-vitreous. Eyes were analyzed for intraocular bacterial growth, retinal function, and inflammation by published methods. Purified B. cereus flagellin was also injected into the mid-vitreous of wild type C57BL/6J mice and inflammation was analyzed. TLR5 activation by B. cereus flagellin was also analyzed in vitro. B. cereus grew rapidly and at similar rates in infected eyes of C57BL/6J and TLR5−/− mice. A significant loss in retinal function in both groups of mice was observed at 8 and 12 hours postinfection. Retinal architecture disruption and acute inflammation (neutrophil infiltration and proinflammatory cytokine concentrations) increased and were significant at 8 and 12 hours postinfection. Acute inflammation was comparable in TLR5−/− and C57BL/6J mice. Physiological concentrations of purified B. cereus flagellin caused significant inflammation in C57BL/6J mouse eyes, but not to the extent of that observed during active infection. Purified B. cereus flagellin was a weak agonist for TLR5 in vitro. These results demonstrated that the absence of TLR5 did not have a significant effect on the evolution of B. cereus endophthalmitis. This disparity may be due to sequence differences in important TLR5 binding domains in B. cereus flagellin or the lack of flagellin monomers in the eye to activate TLR5 during infection. Taken together, these results suggest a limited role for flagellin/TLR5 interactions in B. cereus endophthalmitis. Based on this and previous data, the importance of flagella in this disease lies in its contribution to the motility of the organism within the eye during infection.

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Toll-like receptors in ocular surface diseases: overview and new findings

Cited by 51 publications

References 84 publications

Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6

Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

Role of TLR5 and Flagella in Bacillus Intraocular Infection

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