Interactions of Neutrophils with the Polymeric Molecular Components of the Biofilm Matrix in the Context of Implant-Associated Bone and Joint Infections

Abstract

In the presence of orthopedic implants, opportunistic pathogens can easily colonize the biomaterial surfaces, forming protective biofilms. Life in biofilm is a central pathogenetic mechanism enabling bacteria to elude the host immune response and survive conventional medical treatments. The formation of mature biofilms is universally recognized as the main cause of septic prosthetic failures. Neutrophils are the first leukocytes to be recruited at the site of infection. They are highly efficient in detecting and killing planktonic bacteria. However, the interactions of these fundamental effector cells of the immune system with the biofilm matrix, which is the true interface of a biofilm with the host cells, have only recently started to be unveiled and are still to be fully understood. Biofilm matrix macromolecules consist of exopolysaccharides, proteins, lipids, teichoic acids, and the most recently described extracellular DNA. The latter can also be stolen from neutrophil extracellular traps (NETs) by bacteria, who use it to strengthen their biofilms. This paper aims to review the specific interactions that neutrophils develop when they physically encounter the matrix of a biofilm and come to interact with its polymeric molecular components.

Emerging Issues and Initial Insights into Bacterial Biofilms: From Orthopedic Infection to Metabolomics

“…The extracellular polymeric substance (EPS) of the biofilm is mainly composed of polysaccharides, proteins, teichoic acids, and extracellular DNA. [10,27]. The principal polysaccharide is the Polysaccharide Intercellular Adhesin (PIA), a linear homoglycan composed of β-1,6-linked N-acetylglucosamine residues.…”

“…eDNA strengthens the biofilm, acts as a gene pool for horizontal gene transfer, serves as a source of nutrients, and prevents phagocytosis [43,46,47]. Moreover, eDNA contributes to the complex architecture of the bacterial biofilm matrix through a variety of interactions with other molecular components of the biofilm matrix [27,46].…”

“…MDSCs produce the immunosuppressive molecule interleukin-10 (IL-10), which attenuates the immune response and contributes to biofilm persistence. Some bacteria within biofilms can be phagocytosed by immune cells but resist ROS and AMPs (such as defensins 3 and LL-37) thanks to the polysaccharides of their matrix [27,[143][144][145]. They can survive intracellularly, thus contributing to the chronic nature of biofilm-associated infections.…”

Beyond the double helix: the multifaceted landscape of extracellular DNA in Staphylococcus aureus biofilms

“…Not all of the roles of eDNA are helpful to the biofilm—it can also act as a pathogen-associated molecular pattern (PAMP). Bacterial eDNA can be recognized by the innate immune system by toll-like receptors, particularly TLR9, which is triggered upon phagocytosis of eDNA ( Knuefermann et al., 2007 ; Campoccia et al., 2023 ). One group found that the treatment of P. aeruginosa biofilms with DNase I reduced the ability of the biofilm to upregulate neutrophil activation markers and reduced the release of neutrophil proinflammatory cytokines ( Fuxman Bass et al., 2010 ).…”