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This review summarizes current knowledge on the pathogen\u2013host interactions and immune responses. Early infection can be influenced by tick saliva, which suppresses local host defense and promotes spirochete survival, and by pattern recognition receptors activating proinflammatory cascades.\n                    <jats:italic>Bb<\/jats:italic>\n                    sl employs a variety of immune evasion strategies, notably impairing antigen presentation\u2014through disruption of MHC II and IFN\u2010\u03b3 pathways\u2014and continuously varying surface antigens to hinder long\u2010lasting antibody formation. Autophagy plays a central role in modulating inflammation and T helper 17 adaptive immune responses, representing an underappreciated mechanism potentially influencing disease outcome. Adaptive immunity in LB is characterized by robust but often dysregulated humoral and cellular responses, with transient germinal centers and enduring IgM production contributing to incomplete pathogen clearance. Persistent immune defects include impaired long\u2010term B cell memory, suppressed T cell activation, and ongoing immunosuppression after pathogen clearance. Similar patterns are observed in other postinfectious fatigue syndromes. Despite advances, gaps remain in understanding mechanisms of\n                    <jats:italic>Bb<\/jats:italic>\n                    sl persistence and the immunopathology underlying chronic disease, challenging diagnosis and therapy. Emerging molecular and cellular approaches offer new avenues to address immunity, diagnostics, and prevention. A multidisciplinary effort will be needed to improve long\u2010term patient outcomes in the evolving epidemiology of LB.\n                  <\/jats:p>","DOI":"10.1002\/eji.70195","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:33:18Z","timestamp":1777959198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Borrelia burgdorferi<\/i>\n                    sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System"],"prefix":"10.1002","volume":"56","author":[{"given":"Zara","family":"Karami","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Radboud Community for Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadewych J. M. ter","family":"Hofstede","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Radboud Community for Infectious Diseases (RCI) Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. 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