Demodex-associated bacterial proteins induce neutrophil activation

Abstract

SummaryBackground Patients with rosacea demonstrate a higher density of Demodex mites in their skin than do controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea, thus suggesting a possible role for bacterial proteins in the aetiology of this condition. Objectives To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods Bacterial cells were lysed and proteins were partially purified by Ä KTA fast protein liquid chromatography. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of matrix metalloprotease 9, an enzyme known to degrade collagen, and cathelicidin, an antimicrobial peptide. In addition, neutrophils exposed to the bacterial proteins demonstrated elevated rates of interleukin 8 and tumour necrosis factor-a production. Conclusions Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

Potential role of Demodex mites and bacteria in the induction of rosacea

“…On the skin of humans, this bacterium may occur in the endospore form, which enters the digestive tract of Demodex mites when they consume epithelial cells. The dead mites then decompose inside the hair follicles, where they release significant numbers of bacterial antigens, which have the potential to stimulate a strong immune response (O'Reilly et al, 2012). Thus, the intensification of blepharitis and rosacea, especially the papulopustular variant, may not be induced so much by the presence of the mites alone but by the presence of Demodex mites that carry B. oleronius in their digestive tract.…”

“…Interestingly, inflammation in papulopustular rosacea is often orientated around the pilosebaceous unit, suggesting that the focus of the inflammation is within or adjacent to the unit (Lacey et al, 2007). Exposure of corneal epithelial cells to Bacillus proteins results in an aberrant wound healing response, suggesting a possible link between the action of these antigens on the corneal surface and the development of sterile ulcers which are a common feature of ocular rosacea (O'Reilly et al, 2012).…”

“…Recent work has indicated that a range of B. oleronius proteins can activate neutrophils which migrate and produce inflammatory cytokines. It was speculated that the release of B. oleronius from dead Demodex mites within the pilosebaceous unit could lead to the release of a range of Bacillus proteins into the unit, which 'leak' into the surrounding tissue and so attract neutrophils (O'Reilly et al, 2012). If this occurs in vivo it would lead to inflammation and tissue degradation in the vicinity of the pilosebaceous unit.…”

Rosacea – new data on pathogenesis and treatment

“…Znacznie większa częstość pobudzania komó-rek jednojądrzastych u pacjentów z rosacea może wskazywać na to, że ich układ immunologiczny mógł mieć wcześniejszy kontakt z antygenami Bacillus oleronius [24]. Białka pochodzące od tej bakterii mogą stanowić czynnik aktywujący neutrofile [25].…”

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

“…Exposure of neutrophils to the bacterial proteins resulted in elevated production of IL-8 and TNF-a. 18 Increased production of IL-8 is a trigger for neutrophil recruitment to the site of infection, and TNF-a is indicative of an inflammatory response. These studies suggest a possible role for bacterial proteins in the etiology of rosacea.…”