Abstract
The present concept of the transmission of Lyme disease from Borrelia-infected Ixodes sp. ticks to the naïve host assumes that a low number of spirochetes that manage to penetrate the midgut epithelium migrate through the hemocoel to the salivary glands and subsequently infect the host with the aid of immunomodulatory compounds present in tick saliva. Therefore, humoral and/or cellular immune reactions within the tick hemocoel may play an important role in tick competence to act as a vector for borreliosis. To test this hypothesis we have examined complement-like reactions in the hemolymph of the hard tick Ixodes ricinus against Borrelia afzelii (the most common vector and causative agent of Lyme disease in Europe). We demonstrate that I. ricinus hemolymph does not exhibit borreliacidal effects comparable to complement-mediated lysis of bovine sera. However, after injection of B. afzelii into the tick hemocoel, the spirochetes were efficiently phagocytosed by tick hemocytes and this cellular defense was completely eliminated by pre-injection of latex beads. As tick thioester-containing proteins (T-TEPs) are components of the tick complement system, we performed RNAi-mediated silencing of all nine genes encoding individual T-TEPs followed by in vitro phagocytosis assays. Silencing of two molecules related to the C3 complement component (IrC3-2 and IrC3-3) significantly suppressed phagocytosis of B. afzelii, while knockdown of IrTep (insect type TEP) led to its stimulation. However, RNAi-mediated silencing of T-TEPs or elimination of phagocytosis by injection of latex beads in B. afzelii-infected I. ricinus nymphs had no obvious impact on the transmission of spirochetes to naïve mice, as determined by B. afzelii infection of murine tissues following tick infestation. This result supports the concept that Borrelia spirochetes are capable of avoiding complement-related reactions within the hemocoel of ticks competent to transmit Lyme disease.
Highlights
Ticks are obligatory blood-feeders capable of transmitting a wide variety of pathogens including viruses, bacteria, protozoa, fungi, or nematodes to their vertebrate hosts (Jongejan and Uilenberg, 2004; De La Fuente et al, 2008)
In this study we focused on molecules of the thioester-containing proteins (TEPs) family, which, in Ixodes sp. ticks, involves representatives of four major classes of TEPs known in invertebrates: (i) three proteins related to C3-complement component; (ii) three different α2-macroglobulins; (iii) one insect-type TEP, and (iv) two macroglobulin-complementrelated (MCR) molecules (Buresova et al, 2011; Urbanova et al, 2015)
Using a recently established laboratory transmission model for B. afzelii, we have examined the role of thioester-containing proteins (T-TEPs) in phagocytosis of spirochetes by tick hemocytes and addressed the question of whether or not this cellular defense plays a role in spirochete transmission from Borrelia-infected I. ricinus nymphs to naïve mice
Summary
Ticks are obligatory blood-feeders capable of transmitting a wide variety of pathogens including viruses, bacteria, protozoa, fungi, or nematodes to their vertebrate hosts (Jongejan and Uilenberg, 2004; De La Fuente et al, 2008). Tick Complement vs Borrelia Spirochetes from the infected tick to the naïve host, including defense mechanisms within the tick midgut, hemocoel, and salivary glands; for review see (Hajdusek et al, 2013). Several tick molecules have been described to play important roles in the Borrelia transmission cycle; reviewed in Hajdusek et al (2013) and Kung et al (2013): Glutathione peroxidase Salp 25D facilitates spirochete acquisition from the infected host (Narasimhan et al, 2007); TROSPA, tick receptor for the outer surface protein A, plays a role in Borrelia long-term persistence within the tick gut (Pal et al, 2004); tre that binds to another outer Borrelia surface lipoprotein, BBE 31, allows crossing of the midgut barrier (Zhang et al, 2011). In addition to tick molecules, transmission of spirochetes is aided by proteins originating from the blood meal, such as host plasminogen that is bound and activated on the spirochete surface, facilitating Borrelia migration through the tick and dissemination in the host (Coleman et al, 1997)
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