Effects of Borrelia on host immune system: Possible consequences for diagnostics
Section snippets
Symptoms
Borrelia infection can result in multi-organ disease and is non-pathognomonic except in subcutaneous presentation such as the erythema migrans (EM) rash. Symptoms range from asymptomatic to debilitating. They can imitate many chronic diseases including motor neurone disease [6], multiple sclerosis [7], Parkinson's disease [8], Alzheimer's [9] and fibromyalgia [10] and CFS [11].
Presentation depends on many factors including the stage of the disease [12] and genospecies (Table 2).
Stages of Borreliosis
Stage 1 (early localised) symptoms can begin within 3 days of the tick bite with flu-like symptoms, fever, headache, myalgia, joint pain, stiff neck, fatigue and EM rash, their occurrence dependent on the genospecies [13] (Table 2).
Stage 2 (early disseminated) occurs weeks to months after initial infection and can present with generalised lymphadenopathy and fatigue. Neurological manifestations may include encephalitis, cranial neuritis, radiculoneuritis, paresis, carditis and migratory
Immune evasion
Micro-organisms have developed sophisticated methods of facilitating survival in host. Borrelia, a spirochete bacterium, has evolved many strategies to ensure survival including utilising arthropod salivary proteins (sialostatin, Sal 15) to assist establishment of infection by inhibiting T and dendritic cells [16], [17]. Borrelia prefers micro-anaerobic environments where the immune surveillance is low such as the CNS, joints and skin. To survive in the host, Borrelia has adopted a
Immune dysregulation
There is a growing body of evidence in literature that indicate the presence of significant immune dysfunction in tick borne infections including Borreliosis. The level of immune dysfunction is determined by the host's immune system, number of tick bites, pathogen load, genospecies, strains and the number of co-infections delivered by the tick [24], [29], [30]. Alteration of Borrelia outer surface proteins (Osp), A–E expression inhibits complement activation which aids to establish infection
Diagnostics
Interpretation of diagnostic results needs be in the context of symptomology, risk of tick exposure and/or travel history. Immune status needs to be considered in diagnosis, particularly in suspected Stage 3 Borreliosis. This may impact on the sensitivity of diagnostic tests that are based upon lymphocyte (B or T cell) mediated immune response to Borrelia.
C6 antigen assay – VlsE C6 peptide assay
The C6 antigen assay (26 mer peptide from the sixth invariable region of VlsE) of B. burgdorferi [61] should be sensitive and specific as this region is conserved across the genus. In USA C6 assay failed to detect 1 out 3 ribosomal spacer defined genotypes of Borrelia [74]. This would translate to 33% failure of the C6 antigen assay in the USA East Coast the centre of B. burgdorferi sensu stricto infection. As a result a single C6 test approach recombinant VslE immunoassay [75], or immunoblot
Direct Diagnostic Techniques
Commonly employed Direct Diagnostic Techniques include culture from tissue specimens, microscopy techniques and Nucleic Acid Amplification Techniques (NAAT).
Summary
Understanding the immune dysregulation induced by Borrelia and co-infections can aid the interpretation of diagnostics and improve diagnosis of Borreliosis. Present diagnostics do not discriminate between different stages of Borreliosis. In addition indirect diagnostics reliant on the immune response assume immuno-competence of the host in all stages of Borreliosis. This document has tried to highlight that apart from immune evasion aided by tick saliva in Stages 1 and 2, there is ongoing
Acknowledgment
Extremely grateful for the contributions of Ann Mitrovic to the compilation and editing of this manuscript.
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