Kernien John F, Johnson Chad J, Nett Jeniel E
Department of Medicine, University of Wisconsin, Madison, WI 53706-1521, USA.
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706-1521, USA.
J Fungi (Basel). 2017 Sep;3(3). doi: 10.3390/jof3030049. Epub 2017 Sep 6.
biofilms are difficult to eradicate due to their resistance to host defenses and antifungal drugs. Although neutrophils are the primary responder to during invasive candidiasis, biofilms resist killing by neutrophils. Prior investigation, with the commonly used laboratory strain SC5314, linked this phenotype to the impaired release of neutrophil extracellular traps (NETs), which are structures of DNA, histones, and antimicrobial proteins involved in extracellular microbial killing. Considering the diversity of biofilms, we examined the neutrophil response to a subset of clinical isolates forming biofilms with varying depths and architectures. Using fluorescent staining of DNA and scanning electron microscopy, we found that inhibition of NET release was conserved across the clinical isolates. However, the dampening of the production of reactive oxygen species (ROS) by neutrophils was strain-dependent, suggesting an uncoupling of ROS and NET inhibition. Our findings show that biofilms formed by clinical isolates uniformly impair the release of NETs. Further investigation of this pathway may reveal novel approaches to augment immunity to biofilm infections.
生物膜难以根除,因为它们对宿主防御和抗真菌药物具有抗性。尽管中性粒细胞是侵袭性念珠菌病期间的主要应答者,但生物膜能抵抗中性粒细胞的杀伤。先前使用常用实验室菌株SC5314进行的研究将这种表型与中性粒细胞胞外陷阱(NETs)释放受损联系起来,NETs是由DNA、组蛋白和参与细胞外微生物杀伤的抗菌蛋白组成的结构。考虑到生物膜的多样性,我们研究了中性粒细胞对形成具有不同深度和结构的生物膜的一部分临床分离株的反应。通过DNA荧光染色和扫描电子显微镜,我们发现临床分离株中NET释放的抑制是保守的。然而,中性粒细胞对活性氧(ROS)产生的抑制是菌株依赖性的,这表明ROS和NET抑制之间存在解偶联。我们的研究结果表明,临床分离株形成的生物膜会一致损害NETs的释放。对该途径的进一步研究可能会揭示增强对生物膜感染免疫力的新方法。