Host Defense Against Implant Infection: The Ambivalent Role of Phagocytosis

Abstract

Bacteria embedded in biofilms resist both antibiotics and host defense mechanisms. However, biofilms are not inherently protected against the attack of phagocytic cells. The weapons that polymorphonuclear neutrophils employ against implant infection are phagocytosis, degranulation, with release of antimicrobial molecules, and formation of Neutrophil Extracellular Traps (NETs). NETs contain DNA, histones, and neutrophil elastase, which enable neutrophils to fulfill their role of limiting both microbial spread and the collateral damage from granular contents. It is not yet clear whether the DNA released by neutrophils would support biofilm formation by adding to bacterial extracellular DNA (eDNA), an integral part of the biofilm extracellular matrix. In spite of the evidence of somewhat effective phagocytosis around an implant infection, biofilm-embedded staphylococci persist, tissue destruction occurs and, in the case of orthopedic implant infection, osteolysis prevails. The mechanism for tissue destruction is based on the infiltration and persistence at the site of infection of neutrophils which are unable to effectively perform phagocytosis, but able to inflict tissue damage and cause osteolysis by the release of proteolytic and collagenolytic enzymes. Phagocytosis thus has an ambiguous and ambivalent role: it carries out an antibacterial strategy and at the same time is responsible for osteolysis.