A joint effort: The interplay between the innate and the adaptive immune system in Lyme arthritis

Abstract

Articular joints are a major target of Borrelia burgdorferi, the causative agent of Lyme arthritis. Despite antibiotic treatment, recurrent or persistent Lyme arthritis is observed in a significant number of patients. The host immune response plays a crucial role in this chronic arthritic joint complication of Borrelia infections. During the early stages of B. burgdorferi infection, a major hinder in generating a proper host immune response is the lack of induction of a strong adaptive immune response. This may lead to a delayed hyperinflammatory reaction later in the disease. Several mechanisms have been suggested that might be pivotal for the development of Lyme arthritis and will be highlighted in this review, from molecular mimicry of matrix metallopeptidases and glycosaminoglycans, to autoimmune responses to live bacteria, or remnants of Borrelia spirochetes in joints. Murine studies have suggested that the inflammatory responses are initiated by innate immune cells, but this does not exclude the involvement of the adaptive immune system in this dysregulated immune profile. Genetic predisposition, via human leukocyte antigen‐DR isotype and microRNA expression, has been associated with the development of antibiotic‐refractory Lyme arthritis. Yet the ultimate cause for (antibiotic‐refractory) Lyme arthritis remains unknown. Complex processes of different immune cells and signaling cascades are involved in the development of Lyme arthritis. When these various mechanisms are fully been unraveled, new treatment strategies can be developed to target (antibiotic‐refractory) Lyme arthritis more effectively.

HLA class II immunopeptidomics reveals that co‐inherited HLA‐allotypes within an extended haplotype can improve proteome coverage for immunosurveillance

“…Thus, the source proteins in the dataset were annotated with disease associations catalogued in UniProt knowledgebase. One of the proteins ‐ matrix metalloproteinase‐9 (MMP‐9/Gelatinase B) is known to be associated with rheumatoid arthritis and idiopathic arthritis [49, 50]. Several naturally presented HLA‐DQ7 restricted peptides from MMP‐9 were identified in this study (Table 2).…”

“…Given the importance of the HLA molecules in immunosurveillance and the corresponding strong association of specific HLA alleles with autoimmune diseases we perused the peptide data for source autoanti- Thus, the source proteins in the dataset were annotated with disease associations catalogued in UniProt knowledgebase. One of the proteins -matrix metalloproteinase-9 (MMP-9/Gelatinase B) is known to be associated with rheumatoid arthritis and idiopathic arthritis [49,50]. Several naturally presented HLA-DQ7 restricted peptides from MMP-9 were identified in this study (Table 2).…”

Immune Transcriptome of Cells Infected with Enterovirus Strains Obtained from Cases of Autoimmune Thyroid Disease

“…When a microbe escapes eradication and succeeds in establishing a persistent infection, it initially causes minor host damage without producing clinical symptoms [ 23 ]. Persistence has advantages for both the host and the microbe but may herald slowly progressing diseases such as cancer and autoimmunity [ 24 , 25 , 26 , 27 ].…”

Rats and the COVID-19 pandemic: Early data on the global emergence of rats in response to social distancing

“…However, stressed or wounded rodents are less likely to groom and keep their fur clean, and thus present a greater hazard to mechanically transmit contagious diseases without being infected themselves 48,49 . Additionally, in the case where rodents transmit pathogens that affect the immune system, such as Lyme disease, then those affected could be at increased risk of a weakened immune response to other pathogens 50,51 . These increased risks to human health support the urgent need for more robust data on rats in cities so that we can adequately track these changes and make informed decisions moving forward regarding management.…”