Exposure of a Corneal Epithelial Cell Line (hTCEpi) to Demodex-Associated Bacillus Proteins Results in an Inflammatory Response

McMahon, Frederick W.; Gallagher, Clair; O'Reilly, Niamh; Clynes, Martin; O’Sullivan, Finbarr; Kavanagh, Kevin

doi:10.1167/iovs.14-15018

Cited by 18 publications

(15 citation statements)

References 40 publications

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“…The potential role of B. oleronius proteins in the development of corneal ulcers was recently investigated by exposing corneal epithelial cells (hTCEpi) to Bacillus proteins and this resulted in the upregulation of several pro-inflammatory cytokines including IL-6, IL-8, IL-1b and TNF-a [41]. In a separate study using the same cell line, significant upregulation of MMP3 and MMP9 was observed by cells exposed to B. oleronius, thus leading to a possible explanation for the corneal ulcer formation and corneal scarring in individuals suffering from ocular rosacea [42].…”

Section: The Potential Role Of Bacteria In Rosaceamentioning

confidence: 99%

The role of altered cutaneous immune responses in the induction and persistence of rosacea

Margalit

Kowalczyk

Żaba

et al. 2016

Journal of Dermatological Science

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Rosacea is a chronic inflammatory skin condition that predominantly affects the skin of the face and the eyes. Several factors are associated with the onset and persistence of the condition, including an altered immune response in the skin and elevated levels of Demodex mites. Alterations in the immune response include elevated levels of LL-37 in rosacea skin, increased expression of TLR-2 and increased amounts of vitamin D3 in epidermal tissue. The combined effect of these changes may make the skin more sensitive to external and internal stimuli. External stimuli that may trigger or sustain rosacea inflammation include exposure to ultraviolet light, while internal factors may include the presence of elevated numbers of Demodex mites. These mites may directly stimulate an immune response or release bacteria within the pilosebaceous unit that act as a trigger for inflammation. This review will highlight the changes that occur in the immune response of the skin and describe how Demodex mites and associated bacteria may activate this response and lead to the characteristics of rosacea.

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Section: The Potential Role Of Bacteria In Rosaceamentioning

confidence: 99%

The role of altered cutaneous immune responses in the induction and persistence of rosacea

Margalit

Kowalczyk

Żaba

et al. 2016

Journal of Dermatological Science

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“…While D. brevis was positive in the majority of patients with corneal manifestation [ 15 ], in our study D. folliculorum was detected in all patients except in 1 patient who had D. brevis and D. folliculorum together. Previous studies reported that Bacillus oleronius proteins were found in the Demodex mite, and emphasized that these Bacillus proteins delay healing of wounds, which may hence cause inflammation, non-healing keratitis, and scar formation in the demodulated patients [ 28 , 29 ]. In their study of corneal abnormalities in Demodex patients, Kheirkah et al [ 27 ] found that while D. folliculorum was detected in all of the 6 patients who were found to have anterior blepharitis and CD, D. brevis was detected only in 3 patients.…”

Section: Discussionmentioning

confidence: 99%

A Clinical Scoring System for Diagnosis of Ocular Demodicosis

et al. 2017

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BackgroundDemodex may cause chronic and refractory blepharitis with associated ocular surface problems, and its diagnosis and treatment can be quite challenging. In this study, our aim was to assess the efficacy of tea tree oil in Demodex treatment on caucasian patients in an industrialized region of Turkey, and to develop a systematic scoring system for extremely accurate diagnosis in the absence of advanced facilities.Material/MethodsCharts of 412 patients with blepharitis were reviewed. A group of 39 out of 412 cases were identified as chronic and treatment-refractory, and therefore were enrolled in this study. Eyelashes from each of the lower and upper eyelids of both eyes were evaluated at ×40 and ×100 magnification using light microscopy. Treatment was started with 4% tea tree oil eyelid gel and 10% eyelash shampoo. Symptoms and findings were scored according to the most common complaints.ResultsThe mean age of the patients was 54.1±15.4 years. Seventeen (43.5%) patients were male and 22 (56.5%) patients were female. In 30 out of the 39 patients (76.9%) D. folliculorum was detected. Symptoms disappeared in 25 patients. The mean score of patients who were Demodex-negative was 2.7±1.0, and the mean score of patients who were Demodex-positive was 3.8±1.6 (p=0.047). Ninety-four percent of those with a score of 4 and over were found to be Demodex-positive (p=0.025).ConclusionsTreatment with tea tree oil can be successful. If there is no facility to identify Demodex under light microscopy, we recommend starting treatment for patients who have scores of 4 and over using the scoring chart developed in this study.

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“…oleronius cells were incubated at 30°C and 200 rpm in nutrient broth (Oxoid) under aerobic conditions to the stationary phase, and proteins were extracted and purified as described [25]. The protein preparation was purified by anion exchange separation by ÄKTA-FPLC as described [33]. Fractions corresponding to the proteins of interest were pooled, precipitated (termed pure B. oleronius protein) and resuspended in phosphatebuffered saline (PBS) at a concentration of 200 μg/ml.…”

Section: Preparation Of Bacterial Protein Preparationsmentioning

confidence: 99%

“…Fractions corresponding to the proteins of interest were pooled, precipitated (termed pure B. oleronius protein) and resuspended in phosphatebuffered saline (PBS) at a concentration of 200 μg/ml. Based on previous studies investigating the effects of the B. oleronius protein preparations, two doses (2 and 6 μg/ml) of the crude and pure protein preparations were employed here [25,33,34].…”

Section: Preparation Of Bacterial Protein Preparationsmentioning

confidence: 99%

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Activation of Neutrophils via IP3 Pathway Following Exposure to Demodex-Associated Bacterial Proteins

McMahon¹,

Banville²,

Bergin³

et al. 2015

Inflammation

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Rosacea is a chronic inflammatory condition that predominantly affects the skin of the face. Sera from rosacea patients display elevated reactivity to proteins from a bacterium (Bacillus oleronius) originally isolated from a Demodex mite from a rosacea patient suggesting a possible role for bacteria in the induction and persistence of this condition. This work investigated the ability of B. oleronius proteins to activate neutrophils and demonstrated activation via the IP3 pathway. Activated neutrophils displayed increased levels of IP1 production, F-actin formation, chemotaxis, and production of the pro-inflammatory cytokines IL-1β and IL-6 following stimulation by pure and crude B. oleronius protein preparations (2 μg/ml), respectively. In addition, neutrophils exposed to pure and crude B. oleronius proteins (2 μg/ml) demonstrated increased release of internally stored calcium (Ca(2+)), a hallmark of the IP3 pathway of neutrophil activation. Neutrophils play a significant role in the inflammation associated with rosacea, and this work demonstrates how B. oleronius proteins can induce neutrophil recruitment and activation.

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Exposure of a Corneal Epithelial Cell Line (hTCEpi) to Demodex-Associated Bacillus Proteins Results in an Inflammatory Response

Cited by 18 publications

References 40 publications

The role of altered cutaneous immune responses in the induction and persistence of rosacea

The role of altered cutaneous immune responses in the induction and persistence of rosacea

A Clinical Scoring System for Diagnosis of Ocular Demodicosis

Activation of Neutrophils via IP3 Pathway Following Exposure to Demodex-Associated Bacterial Proteins

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