BACKGROUND: Transmission of pathogens by ticks is greatly supported by tick saliva released during feeding. Dendritic cells (DC) act as immunological sentinels and interconnect the innate and adaptive immune system. They control polarization of the immune response towards Th1 or Th2 phenotype. We investigated whether salivary cystatins from the hard tick Ixodes scapularis, sialostatin L (Sialo L) and sialostatin L2 (Sialo L2), influence mouse dendritic cells exposed to Borrelia burgdorferi and relevant Toll-like receptor ligands. METHODS: DCs derived from bone-marrow by GM-CSF or Flt-3 ligand, were activated with Borrelia spirochetes or TLR ligands in the presence of 3 μM Sialo L and 3 μM Sialo L2. Produced chemokines and IFN-β were measured by ELISA test. The activation of signalling pathways was tested by western blotting using specific antibodies. The maturation of DC was determined by measuring the surface expression of CD86 by flow cytometry. RESULTS: We determined the effect of cystatins on the production of chemokines in Borrelia-infected bone-marrow derived DC. The production of MIP-1α was severely suppressed by both cystatins, while IP-10 was selectively inhibited only by Sialo L2. As TLR-2 is a major receptor activated by Borrelia spirochetes, we tested whether cystatins influence signalling pathways activated by TLR-2 ligand, lipoteichoic acid (LTA). Sialo L2 and weakly Sialo L attenuated the extracellular matrix-regulated kinase (Erk1/2) pathway. The activation of phosphatidylinositol-3 kinase (PI3K)/Akt pathway and nuclear factor-κB (NF-κB) was decreased only by Sialo L2. In response to Borrelia burgdorferi, the activation of Erk1/2 was impaired by Sialo L2. Production of IFN-β was analysed in plasmacytoid DC exposed to Borrelia, TLR-7, and TLR-9 ligands. Sialo L, in contrast to Sialo L2, decreased the production of IFN-β in pDC and also impaired the maturation of these cells. CONCLUSIONS: This study shows that DC responses to Borrelia spirochetes are affected by tick cystatins. Sialo L influences the maturation of DC thus having impact on adaptive immune response. Sialo L2 affects the production of chemokines potentially engaged in the development of inflammatory response. The impact of cystatins on Borrelia growth in vivo is discussed.

• MeSH
• Borrelia burgdorferi immunology   MeSH
• Cystatins pharmacology   MeSH
• Dendritic Cells drug effects   physiology   MeSH
• Ixodes physiology   MeSH
• Teichoic Acids MeSH
• Lipopolysaccharides MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Signal Transduction physiology   MeSH
• Saliva chemistry   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cystatins MeSH
• Teichoic Acids MeSH
• Lipopolysaccharides MeSH
• lipoteichoic acid MeSH Browser
• sialostatin L, Ixodes scapularis MeSH Browser

Selected cerebrospinal-fluid (CSF) parameters (intrathecal synthesis of Borrelia-specific antibodies, oligoclonal IgG bands, CSF-to-serum quotient of albumin as a marker of blood-CSF barrier function and cytology) and typical CSF profile in neuroborreliosis were evaluated with the aim of elucidating possible clinical and laboratory similarities of neuroborreliosis (NB) and other neurological diseases (OND). From the cohort of 58 patients (38 diagnosed for NB, 20 with OND) NB patients had positive Borrelia-specific IgG antibodies in 97 % and positive Borrelia-specific IgM antibodies in 55 %; oligoclonal IgG bands were detected in 55%. The blood-CSF barrier was impaired in 89%, positive cytology was detected in 97% of the NB patients. Evaluation of specific intrathecal synthesis improves CSF diagnosis of NB, therefore, a combined CSF analysis has to be considered along with the clinical picture and medical history when formulating the diagnosis of NB.

• MeSH
• Borrelia burgdorferi Group * immunology   MeSH
• Diagnosis, Differential MeSH
• Blood-Brain Barrier MeSH
• Histocytochemistry MeSH
• Immunoglobulin G cerebrospinal fluid   MeSH
• Immunoglobulin M cerebrospinal fluid   MeSH
• Humans MeSH
• Lyme Neuroborreliosis cerebrospinal fluid   diagnosis   MeSH
• Cerebrospinal Fluid * chemistry   cytology   immunology   MeSH
• Nervous System Diseases cerebrospinal fluid   diagnosis   MeSH
• Antibodies, Bacterial cerebrospinal fluid   MeSH
• Serum Albumin cerebrospinal fluid   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Antibodies, Bacterial MeSH
• Serum Albumin MeSH