Increased Expression of Hepcidin and Toll-Like Receptors 8 and 10 in Viral Keratitis

Mohammed, Imran; Abedin, A; Tsintzas, Kostas; Abedin, S. Asad; Otri, Ahmad Muneer; Hopkinson, Andrew; Mathew, Manu; Dua, Harminder S.

doi:10.1097/ico.0b013e31820126e5

Cited by 24 publications

(21 citation statements)

References 34 publications

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“…34 There are few prior reports on hepcidin response following local, as opposed to systemic infection other than in the gastro-intestinal tract during colitis, 35 and in viral keratitis. 36 The mechanisms are unclear but in vivo studies implicate host induction of local acute phase response proteins and evidence of a host-imposed metal ion limited environment. 37 Hepcidin expression is inhibited in states of iron deficiency.…”

Section: Discussionmentioning

confidence: 99%

Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinabé women

et al. 2019

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BACKGROUND/OBJECTIVES: The iron-binding affinity of vaginal lactoferrin (Lf) reduces iron available to genital pathogens. We describe host reproductive, nutritional, infection and iron biomarker profiles affecting vaginal Lf concentration in young nulliparous and primigravid women in Burkina Faso. SUBJECTS/METHODS: Vaginal eluates from women who had participated in a randomized, controlled periconceptional iron supplementation trial were used to measure Lf using a competitive double sandwich ELISA. For this analysis samples from both trial arms were combined and pregnant and non-pregnant cohorts compared. Following randomization Lf was measured after 18 months (end assessment) for women remaining non-pregnant, and at two antenatal visits for those becoming pregnant. Associations between log Lf levels and demographic, anthropometric, infection and iron biomarker variables were assessed using linear mixed models. RESULTS: Lf samples were available for 712 non-pregnant women at end assessment and for 303 women seen at an antenatal visit. Lf concentrations of pregnant women were comparable to those of non-pregnant, sexually active women. Lf concentration increased with mid-upper-arm-circumference, (P=0.047), body mass index, (P=0.018), Trichomonas vaginalis (P<0.001) infection, bacterial vaginosis (P<0.001), serum C-reactive protein (P=0.048) and with microbiota community state types III/IV. Adjusted Lf concentration was positively associated with serum hepcidin (P=0.047), serum ferritin (P=0.018) and total body iron stores (P= 0.042). There was evidence that some women maintained persistently high or low Lf concentrations from before, and through, pregnancy. CONCLUSION: Lf concentrations increased with genital infection, higher BMI, MUAC, body iron stores and hepcidin suggesting nutritional and iron status influence homeostatic mechanisms controlling vaginal Lf responses.

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Section: Discussionmentioning

confidence: 99%

Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinabé women

et al. 2019

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“…Of these ten, TLR2, 3, 4, 5, and 7 were confirmed at the protein level (Redfern and McDermott, 2010). However, no significant changes on the transcriptional levels of TLRs 1–10 were found in corneal and conjunctival impression cytology samples from DED patients (Mohammed et al, 2011). Our unpublished data on a murine DED model showed no significant change of TLR4 mRNA level, but increased cell surface expression of TLR4 protein on corneal epithelium.…”

Section: Failure Of Ocular Surface Immunohomeostasismentioning

confidence: 93%

Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease

Barabino

Chen

Chauhan

et al. 2012

Progress in Retinal and Eye Research

258

180

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The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others’ studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation.

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“…Tolllike receptors (TLRs) initially recognize bacterial components and induce an inflammatory response in an attempt to clear the pathogen. TLRs are important in mounting an ocular inflammatory response to bacteria during keratitis (17)(18)(19)(20), uveitis (21)(22)(23)(24), and endophthalmitis (25)(26)(27). During Bacillus endophthalmitis, TLRmediated bacterial recognition results in proinflammatory mediator synthesis and an influx of polymorphonuclear neutrophils (PMN), which have the potential to cause irreversible bystander damage to interior tissues of the eye.…”

mentioning

confidence: 99%

Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria

et al. 2015

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Inflammation caused by infection with Gram-positive bacteria is typically initiated by interactions with Toll-like receptor 2 (TLR2). Endophthalmitis, an infection and inflammation of the posterior segment of the eye, can lead to vision loss when initiated by a virulent microbial pathogen. Endophthalmitis caused by Bacillus cereus develops as acute inflammation with infiltrating neutrophils, and vision loss is potentially catastrophic. Residual inflammation observed during B. cereus endophthalmitis in TLR2 ؊/؊ mice led us to investigate additional innate pathways that may trigger intraocular inflammation. We first hypothesized that intraocular inflammation during B. cereus endophthalmitis would be controlled by MyD88-and TRIF-mediated signaling, since MyD88 and TRIF are the major adaptor molecules for all bacterial TLRs. In MyD88 ؊/؊ and TRIF ؊/؊ mice, we observed significantly less intraocular inflammation than in eyes from infected C57BL/6J mice, suggesting an important role for these TLR adaptors in B. cereus endophthalmitis. These results led to a second hypothesis, that TLR4, the only TLR that signals through both MyD88 and TRIF signaling pathways, contributed to inflammation during B. cereus endophthalmitis. Surprisingly, B. cereus-infected TLR4 ؊/؊ eyes also had significantly less intraocular inflammation than infected C57BL/6J eyes, indicating an important role for TLR4 in B. cereus endophthalmitis. Taken together, our results suggest that TLR4, TRIF, and MyD88 are important components of the intraocular inflammatory response observed in experimental B. cereus endophthalmitis, identifying a novel innate immune interaction for B. cereus and for this disease. Bacillus cereus is a Gram-positive, spore-forming, and beta-hemolytic soil bacterium (1). Commonly identified as a causative agent of foodborne illnesses, B. cereus is also associated with a multitude of clinical conditions, such as central nervous system infections (2), pneumonia (3), endocarditis (4), and gas-gangrene-like cutaneous infections (5). B. cereus also causes a virulent form of endophthalmitis, an intraocular inflammatory condition resulting from the introduction of microorganisms into the posterior segment of the eye following surgery or injury or from a distant site of infection. This infection causes irreversible damage to the retina, often leading to vision loss within 1 or 2 days (6). Typically, B. cereus endophthalmitis occurs following a penetrating eye injury (posttraumatic) with retained intraocular foreign bodies (7, 8) but has also been reported in postoperative patients (9-11). Fewer than 30% of posttraumatic B. cereus endophthalmitis patients retained useful vision, and out of these, only 9% retained 20/70 vision or better (7, 12). Moreover, 48% of B. cereus and other Bacillus species infections required evisceration or enucleation of the eye despite therapeutic intervention (7, 12). Intraocular inflammation that occurs during B. cereus endophthalmitis interferes with the clarity of the visual axis, contributing to disruption...

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Increased Expression of Hepcidin and Toll-Like Receptors 8 and 10 in Viral Keratitis

Abstract: Increased expression of LEAP-1 and TLRs 8 and 10 in viral keratitis is novel; TLR-10 has not previously had a documented ligand. LEAP-2 may have a role in dry eye. Further studies will help to improve the understanding of these diseases and yield novel therapeutic interventions.

Cited by 24 publications

References 34 publications

Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinabé women

Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinabé women

Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease

Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with Gram-Positive Bacteria

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