Neutrophil extracellular traps in the fight against biofilm-forming microorganisms: hunters or prey?

Abstract

The review presents up-to-date data on the relationships between neutrophil extracellular traps (NETs) and biofilm-forming microorganisms P aeruginosa, S. aureus, Candida spp. obtained in vitro and in vivo studies. Up to 80% of human microbial infections are associated with biofilm-forming microorganisms. The formation of highly specialized biofilm communities is one of the main strategies for the survival of bacteria and fungi, significantly increasing their tolerance to aggressive and stressful environmental conditions, chemotherapeutic drugs, and immune system factors, contributing to their persistence and chronicity of the infectious process. The formation of NETs in the process of NETosis is one of the biological mechanisms used by neutrophils in protection against pathogens. Chemoattractants of biofilm origin, as well as those secreted by epithelial and immunocompetent cells, attract and activate migrating neutrophils. However, given that bacteria form fairly large cell clusters and aggregates in biofilms, the process of phagocytosis is sometimes difficult or impossible. Under these conditions, it is logical to assume that the importance of NETs in anti-biofilm immunity increases. However, due to the components of the extracellular biofilm matrix (e.g., Psl exopolysaccharide P aeruginosa), quorum sensing (QS) molecules (e.g., LasR QS system P aeruginosa), enzymes (e.g., LasA protease and LasB elastase P. aeruginosa), toxins (e.g., Panton-Valentine leukocidin and AB Y-hemolysin S. aureus) and probably other factors yet to be studied, the microorganisms in biofilms are able to influence the signaling systems involved in NETosis, the intensity of the formation of NETs, the sequestration and killing mechanisms in them, sometimes subordinating and using NETs components for their own purposes.