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- Abu-Humaidan, Anas H., et al.
(författare)
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Persistent intracellular Staphylococcus aureus in keratinocytes lead to activation of the complement system with subsequent reduction in the intracellular bacterial load
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:MAR
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation. Using fluorescence microscopy, we found that persistent SA, surviving intracellularly in keratinocytes, caused activation of the complement system with formation of the terminal complement complex (TCC) at the cell surface. Skin samples from atopic dermatitis patients analyzed by bacterial culture and microscopy, demonstrated that SA colonization was associated with the presence of intracellular bacteria and deposition of the TCC in epidermis in vivo. Complement activation on keratinocytes with persistent intracellular bacteria was found with sera deficient/depleted of the complement components C1q, Mannan-binding lectin, or complement factor B, demonstrating involvement of more than one complement activation pathway. Viable bacterial counts showed that complement activation at the cell surface initiated cellular responses that significantly reduced the intracellular bacterial burden. The use of an inhibitor of the extracellular signal-regulated kinase (ERK) abrogated the complement-induced reduction in intracellular bacterial load. These data bridge the roles of the complement system in tissue homeostasis and innate immunity and illustrate a novel mechanism by which the complement system combats persistent intracellular bacteria in epithelial cells.
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| 2. |
- Bjerkan, Louise, et al.
(författare)
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Multiple functions of the new cytokine-based antimicrobial peptide thymic stromal lymphopoietin (TSLP)
- 2016
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 9:3
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Forskningsöversikt (refereegranskat)abstract
- Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.
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| 3. |
- Gauffin, Håkan, et al.
(författare)
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Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms A 3-Year Follow-up of a Prospective, Randomized Study
- 2017
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Ingår i: American Journal of Sports Medicine. - : SAGE PUBLICATIONS INC. - 0363-5465 .- 1552-3365. ; 45:9, s. 2077-2084
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal treatment for middle-aged patients with knee pain and meniscal lesions has been extensively debated. Most previous studies have revealed only short-term beneficial results of knee arthroscopic surgery. The authors have previously shown a positive benefit of knee arthroscopic surgery and an exercise program after 1 year when compared with an exercise program alone. Purpose: To evaluate if knee arthroscopic surgery combined with an exercise program provided an additional long-term benefit after 3 years compared with an exercise program alone in middle-aged patients with meniscal symptoms. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 179 eligible patients, aged 45 to 64 years, 150 were randomized to (1) a 3-month exercise program (nonsurgery group) or (2) the same as group 1 plus knee arthroscopic surgery within 4 weeks (surgery group). The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscore of pain between baseline and the 3-year follow-up. Results from the 1-year follow-up have been published previously. Results: Both treatment groups improved significantly in the KOOS pain subscore at 3 years follow-up in the intention-to-treat and as-treated analyses (P amp;lt; .001). The between-group difference for the change in the KOOS pain subscore between baseline and the 3-year follow-up was no longer statistically significant, neither in the intention-to-treat analysis (7.6 points; 95% CI, -0.6 to 15.9; P = .068) nor in the as-treated analysis (5.3 points; 95% CI, -3.1 to 13.8; P = .216). The factorial analysis of the effect of the intervention and age, onset of pain, and mechanical symptoms indicated that older patients improved more, regardless of treatment, and surgery may be more beneficial for patients without mechanical symptoms (as-treated analysis). The effect of the predictive factors on the KOOS pain subscore was uncertain because of the small sample size in the subgroup analyses. Conclusion: The benefit of knee arthroscopic surgery, seen at 1 year in middle-aged patients with meniscal symptoms, was diminished at 3 years and was no longer statistically significant.
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| 4. |
- Saleh, Karim, et al.
(författare)
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Can dressings soaked with polyhexanide reduce bacterial loads in full-thickness skin grafting? A randomized controlled trial
- 2016
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Ingår i: Journal of the American Academy of Dermatology. - : Elsevier BV. - 0190-9622. ; 75:6, s. 4-1228
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Tidskriftsartikel (refereegranskat)abstract
- Background Polyhexamethylene biguanide (PHMB)-based antiseptic solutions can reduce bacterial loads in different clinical settings and are believed to lower risk of infections. Objective We sought to assess the efficacy of a PHMB-based solution in lowering bacterial loads of full-thickness skin grafting wounds and the risk of surgical site infections (SSIs). Methods In this double-blinded clinical trial, 40 patients planned for facial full-thickness skin grafting were randomized 1:1 to receive tie-over dressings soaked with either PHMB-based solution or sterile water. Quantitative and qualitative bacterial analysis was performed on all wounds before surgery, at the end of surgery, and 7 days postoperatively. In addition, all patients were screened for nasal colonization of Staphylococcus aureus. Results Analysis of wounds showed no statistically significant difference in bacterial reductions between the groups. The SSI rates were significantly higher in the intervention group (8/20) than in the control group (2/20) (P = .028). Higher postoperative bacterial loads were a common finding in SSIs (P = .011). This was more frequent when S aureus was present postoperatively (P = .034), intraoperatively (P = .03), and in patients with intranasal S aureus colonization (P = .007). Limitations Assessment of SSIs is largely subjective. In addition, this was a single-center study and the total number of participants was 40. Conclusion Soaking tie-over dressings with PHMB solution in full-thickness skin grafting had no effect on postoperative bacterial loads and increased the risk of SSI development. The presence of S aureus intranasally and in wounds preoperatively and postoperatively increased postoperative bacterial loads, which in turn resulted in significantly more SSIs.
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| 6. |
- Sonesson, Andreas, et al.
(författare)
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Identification of bacterial biofilm and the Staphylococcus aureus derived protease, staphopain, on the skin surface of patients with atopic dermatitis
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus (S. aureus) isolates from lesional skin of patients with AD, produced a substantial amount of biofilm in vitro. S. aureus biofilms showed less susceptibility to killing by the antimicrobial peptide LL-37 when compared with results obtained using planktonic cells. Confocal microscopy analysis showed that LL-37 binds to the S. aureus biofilms. Immuno-gold staining of S. aureus biofilm of AD skin detected the S. aureus derived protease staphopain adjacent to the bacteria. In vitro, staphopain B degraded LL-37 into shorter peptide fragments. Further, LL-37 significantly inhibited S. aureus biofilm formation, but no such effects were observed for the degradation products. The data presented here provide novel information on staphopains present in S. aureus biofilms in vivo, and illustrate the complex interplay between biofilm and LL-37 in skin of AD patients, possibly leading to a disturbed host defense, which facilitates bacterial persistence.
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