Persistent Borrelia burgdorferi Peptidoglycan in Postinfectious Lyme Arthritis: Innate Immune Sensing and Translational Implications
6 affiliations
- 1Primary Health Care, Universidad Anáhuac Xalapa, Xalapa, MEX
- 2Outpatient Care, Universidad de las Américas, Quito, ECU
- 3Outpatient Care, Universidad Anáhuac Xalapa, Veracruz, MEX
- 4Primary Care, Universidad Católica de Santa María, Arequipa, PER
- 5Emergency Department, Hospital Central de la Policía Nacional, Bogotá, COL
- 6Public Health, NeoScientia Consulting Group, Quito, ECU
Abstract
Lyme arthritis (LA) is the late articular manifestation of Borrelia burgdorferi infection. It is ordinarily treated successfully with appropriate antibiotic therapy. In a subset of patients, however, synovitis persists for months to years after treatment, despite presumed eradication of the spirochete. This state is termed postinfectious, or antibiotic-refractory, LA, and its cellular and molecular basis remains incompletely defined. It is distinct from post-treatment Lyme disease syndrome (PTLDS), which is defined by persistent subjective symptoms without objective joint inflammation. Attention has increasingly turned to the non-canonical peptidoglycan (PG) of B. burgdorferi. Three questions are central: what becomes of this material during bacterial growth, whether it persists within the joint after antimicrobial treatment, and whether it can engage innate immune sensing pathways such as NOD2. Whether such sensing occurs in the human joint has yet to be established. This narrative review synthesizes the available human, murine, and in vitro mechanistic evidence on four topics: B. burgdorferi PG biology, PG processing in both the bacterium and the host, the innate mechanisms of PG recognition, and the intersection of these pathways with adaptive autoimmune mechanisms in postinfectious LA. Throughout, findings established in patients are distinguished from inferences drawn from murine models and from hypotheses that remain unsupported by patient-level data. Human evidence is limited to detection of PG in synovial fluid from closely related research groups and is not independently replicated, together with genetic, immunologic, and tissue studies that do not themselves address PG. Findings such as PG tropism for the liver and NOD2 sensing derive from murine and in vitro systems. No study has shown that persistent PG or NOD2 signaling causes human postinfectious synovitis. The authors then consider the translational implications for diagnostic, prognostic, and anti-inflammatory or PG-directed strategies as hypotheses.
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BibTeX
@article{hernandez2026persistent,
title = {{Persistent Borrelia burgdorferi Peptidoglycan in Postinfectious Lyme Arthritis: Innate Immune Sensing and Translational Implications}},
author = {José L. de Jesús Arguello Hernández and Emanuela K Arcos Lema and Carlos A Arragan Lezama and Rodrigo F Ale Chura and María V Fontalvo Leyton and Andrés S Estrella López},
journal = {Cureus},
year = {2026},
month = oct,
doi = {10.7759/cureus.118893},
url = {https://europepmc.org/article/PMC/PMC13723275},
note = {CC BY},
}
RIS
TY - JOUR
TI - Persistent Borrelia burgdorferi Peptidoglycan in Postinfectious Lyme Arthritis: Innate Immune Sensing and Translational Implications
AU - José L. de Jesús Arguello Hernández
AU - Emanuela K Arcos Lema
AU - Carlos A Arragan Lezama
AU - Rodrigo F Ale Chura
AU - María V Fontalvo Leyton
AU - Andrés S Estrella López
PY - 2026
DA - 2026/10/31
JO - Cureus
DO - 10.7759/cureus.118893
UR - https://europepmc.org/article/PMC/PMC13723275
AB - Lyme arthritis (LA) is the late articular manifestation of Borrelia burgdorferi infection. It is ordinarily treated successfully with appropriate antibiotic therapy. In a subset of patients, however, synovitis persists for months to years after treatment, despite presumed eradication of the spirochete. This state is termed postinfectious, or antibiotic-refractory, LA, and its cellular and molecular basis remains incompletely defined. It is distinct from post-treatment Lyme disease syndrome (PTLDS), which is defined by persistent subjective symptoms without objective joint inflammation. Attention has increasingly turned to the non-canonical peptidoglycan (PG) of B. burgdorferi. Three questions are central: what becomes of this material during bacterial growth, whether it persists within the joint after antimicrobial treatment, and whether it can engage innate immune sensing pathways such as NOD2. Whether such sensing occurs in the human joint has yet to be established. This narrative review synthesizes the available human, murine, and in vitro mechanistic evidence on four topics: B. burgdorferi PG biology, PG processing in both the bacterium and the host, the innate mechanisms of PG recognition, and the intersection of these pathways with adaptive autoimmune mechanisms in postinfectious LA. Throughout, findings established in patients are distinguished from inferences drawn from murine models and from hypotheses that remain unsupported by patient-level data. Human evidence is limited to detection of PG in synovial fluid from closely related research groups and is not independently replicated, together with genetic, immunologic, and tissue studies that do not themselves address PG. Findings such as PG tropism for the liver and NOD2 sensing derive from murine and in vitro systems. No study has shown that persistent PG or NOD2 signaling causes human postinfectious synovitis. The authors then consider the translational implications for diagnostic, prognostic, and anti-inflammatory or PG-directed strategies as hypotheses.
SN - 2168-8184
ER -