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Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

ABSTRACT: Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6-deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

SUBMITTER: Zimmermann C

PROVIDER: S-EPMC6789730 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Zimmermann C C Troeltzsch D D Giménez-Rivera V A VA Galli S J SJ Metz M M Maurer M M Siebenhaar F F

Proceedings of the National Academy of Sciences of the United States of America 20190923 41

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to <i>Pseudomonas aeruginosa</i> skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absenc ...[more]

PMID: 31548430

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Project description:Wound infections are serious medical complications that can endanger human health. Latest researches show that conductive composite materials may make endogenous/exogenous electrical stimulation more effective, guide/comb cell migration to the wound, and subsequently promote wound healing. To accelerate infected wound healing, a novel medical silver nanoparticle-doped conductive polymer-based hydrogel system (Ag NPs/CPH) dressing with good conductivity, biocompatibility, and mechanical and antibacterial properties was fabricated. For the hydrogel dressing, Ag NPs/CPH, polyvinyl alcohol (PVA), and gelatin were used as the host matrix materials, and phytic acid (PA) was used as the cross-linking agent to introduce conductive polyaniline into the matrix, with antibacterial Ag NPs loaded via impregnation. After a series of analyses, the material containing 5 wt% of PVA by concentration, 1.5 wt% gelatin, 600 μL of AN reactive volume, and 600 μL of PA reactive volume was chosen for Ag NPs/CPH preparation. XPS and FTIR analysis had been further used to characterize the composition of the prepared Ag NPs/CPH. The test on the swelling property showed that the hydrogels had abundant pores with good water absorption (≈140% within 12 h). They can be loaded and continuously release Ag NPs. Thus, the prepared Ag NPs/CPH showed excellent antibacterial property with increasing duration of immersion of Ag NPs. Additionally, to evaluate in vivo safety, CCK-8 experiments of HaCat, LO2 and 293T cells were treated with different concentrations of the Ag NPs/CPH hydrogel soaking solution. The experimental results showed the Ag NPs/CPH had no significant inhibitory effect on any of the cells. Finally, an innovative infection and inflammation model was designed to evaluate the prepared Ag NPs/CPH hydrogel dressing for the treatment of severely infected wounds. The results showed that even when infected with bacteria for long periods of time (more than 20 h), the proposed conductive antibacterial hydrogel could treat severely infected wounds.

Project description:BackgroundBacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring.ResultsHerein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes.ConclusionsWe think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.

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Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Publications

Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

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