Periprosthetic joint infection and immunity: Current understanding of host–microbe interplay

Abstract

Periprosthetic joint infection is a major complication of total joint arthroplasty. Even with current treatments, failure rates are unacceptably high with a 5‐year mortality rate of 26%. Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, anti‐biofilm agents, and bacteriophages. Nevertheless, the role of the immune system, our first line of defense during PJI, is not well understood. Evidence of infection in PJI patients is found within circulation, synovial fluid, and tissue and include numerous cytokines, metabolites, antimicrobial peptides, and soluble receptors that are part of the PJI diagnosis workup. Macrophages, neutrophils, and myeloid derived suppressor cells (MDSCs) are initially recruited into the joint by chemokines and cytokines produced by immune cells and bacteria and are activated by pathogen‐associated molecular patterns (PAMPs). While these cells are efficient killers of planktonic bacteria by phagocytosis, opsonization, degranulation, and recruitment of adaptive immune cells, biofilm‐associated bacteria are troublesome. Biofilm is not only a physical barrier for the immune system but also elicit effector functions. Additionally, bacteria have developed mechanisms to evade the immune system by inactivating effector molecules, promoting killing or anti‐inflammatory effector cell phenotypes, and intracellular persistence and dissemination. Understanding these shortcomings and the mechanisms by which bacteria can subvert the immune system may open new approaches to better prepare our own immune system to combat PJI. Furthermore, preoperative immune system assessment and screening for dysregulation may aid in developing preventative interventions to decrease PJI incidence.This article is protected by copyright. All rights reserved.

Material-based treatment strategies against intraosseous implant biofilm infection

“…In the presence of endophytes, the local immune milieu is disrupted, while biofilms hinder the activity of peripheral immune cells, particularly antigen-presenting cells (APCs), leading to inadequate antigen presentation and ultimately insufficient immune activation in the host [ [90] , [91] , [92] ]. In contrast to planktonic bacteria, the immunogenicity of bacteria-associated antigens within biofilms is significantly reduced, leading to inadequate antigen recognition and heightened depletion of antigen-presenting cells, T cell suppression, and compromised B cell activation, ultimately resulting in a biofilm-specific immune deficiency [ 90 , 93 ]. Bacteria within biofilms have been shown to indirectly induce immune cell dysfunction by producing elevated levels of peroxides, metabolic toxins, and acidic byproducts, leading to phenomena such as heightened M2 polarization of macrophages and impaired function of dendritic cells, as well as an increase in regulatory Tregs.…”

A Water-Based Biocoating to Increase the Infection Resistance and Osteoconductivity of Titanium Surfaces

“…However, several protective measures in the intraoperative environment, such as the use of plastic adhesive drapes and sterile stockinette, as well as the use of personal protection surgical helmet systems, clearly do not reduce the risk of infection [ 5 , 6 , 7 ]. The antibacterial methods in current clinical use still suffer high failure rates, with a five-year mortality rate of 26%, largely due to the formation of biofilms on implant surfaces by various pathogens [ 8 ]. Consequently, research is increasingly exploring the development of antimicrobial surfaces that can reduce pathogen adhesion on the prosthesis and thus decrease infection, while promoting cellular adhesion and proliferation [ 9 , 10 ].…”