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Majority of the literature in the field has focused on development of better biomarkers for diagnostics and treatment strategies including innovate antibiotic delivery systems, antibiofilm 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\u2010derived suppressor cells (MDSCs)\u00a0are initially recruited into the joint by chemokines and cytokines produced by immune cells and bacteria and are activated by pathogen\u2010associated molecular patterns.\u00a0While these cells are efficient killers of planktonic bacteria by phagocytosis, opsonization, degranulation, and recruitment of adaptive immune cells, biofilm\u2010associated bacteria are troublesome. Biofilm is not only a physical barrier for the immune system but also elicits effector functions. Additionally, bacteria have developed mechanisms to evade the immune system by inactivating effector molecules, promoting killing or anti\u2010inflammatory 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.<\/jats:p>","DOI":"10.1002\/jor.25723","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T10:43:46Z","timestamp":1698144226000},"page":"7-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Periprosthetic joint infection and immunity: Current understanding of host\u2013microbe interplay"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-7538","authenticated-orcid":false,"given":"Nicolas S.","family":"Piuzzi","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Cleveland Clinic Adult Reconstruction Research (CCARR), Cleveland Clinic Cleveland Ohio USA"},{"name":"Department of Biomedical Engineering Cleveland Clinic Cleveland Ohio 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