Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

Abstract

Similarly to other blood-feeding arthropods, ticks have evolved immunosuppressive mechanisms enabling them to overcome the host immune system. Although the immunomodulatory effect of tick saliva on several cell populations of the immune system has been extensively studied, little is known about its impact on dendritic cells (DCs). We have examined the effect of Ixodes ricinus tick saliva on DC function in vitro and in vivo. Exposure of DCs to tick saliva in vitro resulted in impaired maturation, upon CD40 or TLR9, TLR3 and TLR7 ligation, as well as reduced Ag presentation capacity. Administration of tick saliva in vivo significantly inhibited maturation and early migration of DCs from inflamed skin to draining lymph nodes, and decreased the capacity of lymph node DCs to present soluble Ag to specific T cells. Moreover, saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses. Our data reveal a complex inhibitory effect exerted by tick saliva on DC function. Given the role of DCs as the key instigators of adaptive immune responses, alteration of their function might represent a major mechanism of tick-mediated immune evasion.

Ixodes ricinus Salivary Serpin IRS-2 Affects Th17 Differentiation via Inhibition of the Interleukin-6/STAT-3 Signaling Pathway

“…Similar results, showing that tick saliva inhibits the Th17 subset, were reported by Skallova and colleagues, who showed that saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses (42). Interestingly, treatment with Salp15, which also inhibits IL-6 production in dendritic cells, was shown to increase the differentiation of Th17 cells in vivo, as evidenced by higher IL-17 production from PLP139-151-specific CD4 ϩ T cells isolated from the central nervous system and the periphery (43).…”

Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks

“…Many of these mechanisms operating against Borrelia infection are inhibited by molecules present in tick saliva, including complement (Kýčkovaá nd , phagocytosis, and the killing of spirochetes by macrophages (Kuthejlova´et al, 2001), production of proinflammatory cytokines (Ferreira and Silva, 1999;Schoeler et al, 1999), which is connected with the polarization of the host immune response towards the Th2 type (Mejri et al, 2001;Skallova´et al, 2008). It is very likely that the immunomodulatory effect of tick saliva creates more favorable conditions for Borrelia transmission, proliferation, and spreading to target organs (Nuttall and Labuda, 2004).…”

“…Tick saliva was shown to decrease the production of proinflammatory cytokines like IL-1, TNF-a, IFN-g, and increase the elaboration of antiinflammatory cytokines IL-10 or TGF-b (Ramachandra and Wikel, 1992;Ferreira and Silva, 1998;Kopecký et al, 1999). Polarization of the host immune response towards the Th2 subset was reported (Ferreira and Silva, 1999;Schoeler et al, 1999), at least partly, due to the effect of saliva on host dendritic cells (Skallova´et al, 2008). Several molecules responsible for these effects have already been identified, including complement inhibitors, namely Isac (Valenzuela et al, 2000), IRAC 1 and 2 (Schroeder et al, 2007), Salp20 (Tyson et al, 2007), T cell inhibitor Salp15 (Garg et al, 2006), IL-2-binding protein (Gillespie et al, 2001), and CC chemokines-binding protein (Frauenschuh et al, 2007).…”

Prevention of Lyme Disease: Promising Research or Sisyphean Task?

“…Furthermore, DCs exposed to tick saliva decrease the expression of surface B7-2 and major histocompatibility complex leading to impairment of DC-mediated activation of T cells. On the other hand, tick saliva-exposed DC increase the expression of IL-4 and IL-5 (Sa-Nunes et al 2007;Skallova et al 2008). Recent work by several authors focused on elucidation of tick saliva immunomodulatory activity indicates involvement of Raf-1 kinase and mitogen-activated protein kinase pathways activated by binding of tick protein Salp-15 to DC receptor DC-SIGN (CD209) and/or the role of prostaglandin E 2 (Hovius et al 2008;Sa-Nunes et al 2007).…”