Extracellular RNA as a potential activator of Neutrophil Extracellular Traps by Candida albicans biofilm

Abstract

Neutrophils represent the first line of innate host defense. The ability to inhibit the development of infections is associated with the involvement of several fighting strategies. The still poorly understood mechanism is netosis, involving the release of Extracellular Neutrophil Traps (NETs). NETs are complexes of chromosomal DNA and granule content. Such a web-like structure inhibits the spread of invaders. Netosis plays a significant role in combating Candida albicans infections. It has been shown that several factors, composing C. albicans cell surface mediate NETs production. However, the development of difficult to eradicate fungal infection is associated with the formation of the biofilm structure, which partially protects the pathogen cells from contact with the host’s immune system. One of the reasons for the creation of a such protective environment is the production of the extracellular matrix (ECM). The major components of the C. albicans ECM layer are lipids, proteins, carbohydrates but also extracellular nucleic acids, among which we observed a significant RNA content. Considering that the ECM consisting of RNA molecules is one of the first lines of contact between biofilms and neutrophils, our current studies aimed to assess the potential role of extracellular RNA in the triggering of the netosis process by human neutrophils in vitro. We showed that RNA purified from C. albicans biofilm structure and the whole cells have the capability to induction of ROS-dependent netosis pathway. Additionally, cell migration analysis indicate that RNA molecules may also be an effective chemotactic agent. This work was supported by NCN (2019/33/B/NZ6/02284).

Neutrophil Extracellular Traps in Candida albicans Infection

“…Extracellular nucleic acids purified from mature biofilms or nucleic acids isolated from intact fungal cells have the potential to activate neutrophils to release NETs in vitro . These DNA and RNA molecules trigger NET formation through the ROS-dependent pathway, in which TLR8 and TLR9 are involved ( 48 , 49 ). As biofilms form, information is transmitted between C. albicans cells through a quorum sensing (QS) mechanism ( 50 , 51 ) facilitated by QS molecules (QSMs) mainly including farnesoic acid, tyrosol, and farnesol.…”