Horn Adam, Wagner Andrew S, Hou Yiran, Zajac Jocelyn C, Fister Alexandra M, Chen Zhili, Pashaj Joana, Junak Mary, Mercado Soto Nayanna M, Gibson Angela, Huttenlocher Anna
Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Wound Repair Regen. 2025 Jan-Feb;33(1):e13242. doi: 10.1111/wrr.13242.
Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behaviour following burn injury and the subsequent potential for microbial colonisation of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonisation by the fungal pathogen Candida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonisation of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behaviour contributes to burn wound progression in larval zebrafish and links keratinocyte dynamics to microbial colonisation of burn wounded tissue.
烧伤会经历一个复杂的愈合过程,在此过程中,上皮损伤的逐渐扩散会导致诸如伤口感染等继发性并发症,而伤口感染是烧伤患者死亡的主要原因。我们最近报道,与机械损伤相比,烧伤斑马鱼幼体引发了角质形成细胞动力学失调。在此,我们研究烧伤后角质形成细胞的行为以及随着时间推移烧伤伤口随后发生微生物定植的可能性。实时成像结合对光转化细胞的追踪显示,早期角质形成细胞的运动性会导致上皮损伤扩散至烧伤初始部位之外,而上皮损伤增加与真菌病原体白色念珠菌在伤口的定植有关。用等渗培养基处理斑马鱼幼体来调节渗透压平衡,限制了上皮损伤的扩散,并减少了烧伤伤口的微生物定植。利用培养的人类皮肤,我们发现用等渗溶液(生理盐水)进行局部治疗同样能随着时间推移防止上皮损伤的扩散。这些发现表明,角质形成细胞的行为会促使斑马鱼幼体烧伤伤口的进展,并将角质形成细胞动力学与烧伤伤口组织的微生物定植联系起来。