Immune Response to Borrelia
As common Lyme disease tests are based upon serology the immune status of the patient is crucial in interpreting and diagnosing Lyme and other tick borne infections. Immune modulation by the tick saliva is when Borrelia dissemination and establishment in the host is determined.
The entry and early survival of Borrelia into the host is enhanced by proteins and hormones in tick saliva.
The modulatory effects of saliva in the host include:
1. Prevention of phagocytosis and production of superoxide by dendritic cells (13Ribeiro et al 1990).
2. Inhibition of nitric oxide production by macrophages (Urieste et al 1994).
3. Impairment of NK cell function (Kopecky & Kathetlova 1998).
4. Reduction of the antiviral effect of IFN (interferon) (Hajniecka et al 2000).
6. Inhibition of IL-2 function and cytokine cascade (Berende et al 2010).
7. Inhibition of cytotoxic T and B cell function by Sialostatin L (Berende et al 2010, Keane and Irvine 2013).
- Complement Regulator Acquiring Surface Proteins (CRASPs) of Borrelia e.g. (Outer Surface Protein) OspE and OspA, which repress cytolytic activity of the host (Kraiczy et al 2004, de Taeye et al 2013.
- Erp (Extracellular membrane Related Protein) 32kD, which inhibit complement alternate pathway (de Taeye et al 2013).
9. Quorum sensing involves LuxS gene for methylation and use of homocysteine to synthesize Auto Inducer-2 (AI-2) (Stevenson and Babb et al 2002). AI-2, concentration in the cell reaches critical levels that regulate gene activation in synchrony with other members of the biofilm community. This enables bacterial cells to communicate with each other.
Tick saliva and Borrelia manage to paralyse macrophages and prevent the initiation of an effective immune response and allow pathogens to spread in connective tissue. The symbiotic relationship between tick saliva and Borrelia results in predominance of the immune response towards a T helper 2- cytokine profile and inhibition of IFN-g and induction of T cell independent immune response.
In untreated, stage 3 or chronic Lyme disease, the level of immune dysfunction can be determined by the hosts’ immune system, number of tick bites, pathogen load, Borrelia genospecies/strains and the number of co–infections.
In stage 3 or chronic Lyme disease, abnormal levels of antibodies or T cell inactivation can alter the diagnostic outcome. Therefore interpretation of diagnostics, should consider the immune status of the patient especially since multiple tick borne pathogens can also compound immune dysfunction.
In chronic Lyme disease inhibition of Th 1 immune response can result in diminished interferon gamma (IFN-gamma production leading to significant immune dysfunction. Borrelia phagocytised by dendritic cells can alter cellular function including the cytokines released and manipulate the immune system (Dickinson and Alugupalli 2012). The increased production of anti-inflammatory cytokine IL-10 in chronic Lyme disease can facilitate host invasion (Berende et al 2010).
The level of immune suppression can be reflected by the ratio of IFN gamma/IL-10 levels. Tests that may assist a clinician to assess immune system function can include total IgG and all subclasses eg: IgG2b (low affinity) and IgG3 (inhibitory), IgG1, IgE, IgA or IgM levels and lymphocyte markers such as CD57 (NK cell), CD19 (follicular B cells), CD4 (T helper 1 cell), CD8 (cytotoxic T cell), CD40 (isotype switching B cells) and complement C3a and C4a. These biomarkers can help to characterize the diversity of immune dysfunction. (Hawley KL et al 2012, Hawley K et al 2012, Tunev et al 2011)
Growing evidence of an emerging tick-borne disease that causes a Lyme like illness for many Australian patients
On 12 November 2015, the Senate referred the following matter to the Senate Community Affairs References Committee for inquiry and report:
The growing evidence of an emerging tick-borne disease that causes a Lyme‑like illness for many Australian patients.