Characterization of the B‐cell inhibitory protein factor in <i>Ixodes ricinus</i> tick saliva: a potential role in enhanced <i>Borrelia burgdoferi</i> transmission

Hannier, Sigrid; Liversidge, Janet; Sternberg, Jeremy M.; Bowman, Alan K.

doi:10.1111/j.1365-2567.2004.01975.x

Cited by 67 publications

(51 citation statements)

References 30 publications

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“…One microgram of total RNA was reverse transcribed using oligo(dT) [12][13][14][15][16][17][18] and Superscript II reverse transcriptase (GIBCO-Invitrogen). Quantitative real-time PCR was performed in a Bio-Rad (Hercules, CA) iCycler with Bio-Rad iQ SYBR green Supermix.…”

Section: Methodsmentioning

confidence: 99%

“…Especially for ticks, which are characterized by their extended feeding time, a broad repertoire of immune modulatory activities has been described. These modulatory activities include the predominant induction of a Th2 response with an overall inhibition of proinflammatory and Th1 cytokines (23,24,38,54), suppression of the effector functions of antigen-presenting cells (APCs) (5,26,28,59), and modulation of T-cell (28,59) and B-cell (17,18) responses, as well as the inhibition of granulocyte infiltration (39,53) and NK-mediated cytotoxicity (25). Illustrating the importance of salivary components for pathogen transmission, the tick protein Salp15 was shown to significantly increase the infectivity of Borrelia burgdorferi spirochetes in mice (50).…”

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confidence: 99%

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Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

et al. 2006

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Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the African continent. These blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. Here we demonstrate that tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection. This effect was associated with a reduced inflammatory reaction at the site of infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12 mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not suppressed. We propose that tsetse fly saliva accelerates the onset of trypanosome infection by inhibiting local and systemic inflammatory responses involved in parasite control.African trypanosomes are extracellular protozoan flagellates that infect a broad range of vertebrate hosts, including humans, and rely for their transmission on tsetse flies (Glossina sp.), which are obligately blood-feeding organisms (62). In the mammalian host, the parasites establish controlled growth to ensure survival and optimal transmission. In order to escape the adaptive immune system, trypanosomes undergo antigenic variation by altering their major surface antigen, the variantspecific surface glycoprotein (VSG) (6). Beside this immune evasion mechanism, trypanosomes have been shown to modulate immune functions of macrophages (8, 43), T lymphocytes (56), and B lymphocytes (2). The main host immune effectors involved in parasite control are considered to be trypanosomespecific antibodies (30) and the cytokine tumor necrosis factor (TNF) (33). Concerning trypanosome-specific antibodies, increased VSG-reactive immunoglobulin M (IgM) and IgG2a antibody isotypes have been associated with improved control of trypanosome infections (34, 55). TNF, as a host cytokine, was released from activated macrophages in response to stimulation by soluble VSG (sVSG) and membrane-bound VSG (11,35). TNF was demonstrated to have trypanocidal properties for certain trypanosome stocks and to be associated with the occurrence of immune pathology in infected animals (33). As such, direct or indirect modulation of parasite-specific antibody induction and TNF release might influence trypanosome growth and the severity of infection.Focusing on the early stage of trypanosome infection in the mammalian host, the effect of tsetse fly salivary components on parasitemia onset and on the involved host antiparasite immune effectors has been poorly investigated. Studies with other blood-sucking arthropods, such as ticks and sand flies, have demonstrated that salivary proteins are potent modulators of host innate and adaptive immune responses. Especially for ticks, which are characterized by their extended feeding time, a broad repertoire of immune modulatory activities has been...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

et al. 2006

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“…During the feeding process, saliva from the tick accompanies the spirochete into the host tissue. Recent findings have provided clear evidence of roles for various tick salivary factors, such as B cell inhibitory protein (64) and sialostatin L (84), among others (98,106,(121)(122)(123), in the localized disruption of host tissues and immune responses. The activity of these salivary factors supports the successful transmission of B. burgdorferi organisms to the host as well as providing a localized environment by which the spirochetes can evade immune clearance.…”

Section: Development Of Arthritis Upon Infection With B Burgdorferimentioning

confidence: 99%

Lyme Arthritis: Current Concepts and a Change in Paradigm

Nardelli

Callister

Schell

2008

Clin Vaccine Immunol

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“…It has already been shown that they use Salp15 to inhibit the activation and proliferation of CD4 ϩ T cells by binding to its CD4 receptor (1,6,13). In addition, tick salivary proteins have been found to inhibit B cells (8), dendritic cells (4,11), NK cells (17), neutrophils (20), and macrophages (7). Isac (5,27) and Salp20 (26) are two salivary proteins that were shown to inhibit the alternative pathway of the complement system.…”

Section: Discussionmentioning

confidence: 99%

The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates

et al. 2008

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Borrelia burgdorferi, the agent of Lyme disease, is transmitted by ticks. During transmission from the tick to the host, spirochetes are delivered with tick saliva, which contains the salivary protein Salp15. Salp15 has been shown to protect spirochetes against B. burgdorferi-specific antibodies. We now show that Salp15 from both Ixodes ricinus and Ixodes scapularis protects serum-sensitive isolates of Borrelia burgdorferi sensu lato against complement-mediated killing. I. ricinus Salp15 showed strong protective effects compared to those of I. scapularis Salp15. Deposition of terminal C5b to C9 (one molecule each of C5b, C6, C7, and C8 and one or more molecules of C9) complement complexes, part of the membrane attack complex, on the surface of B. burgdorferi was inhibited in the presence of Salp15. In the presence of normal human serum, serum-sensitive Borrelia burgdorferi requires protection against complement-mediated killing, which is provided, at least in part, by the binding to the tick salivary protein Salp15.The Lyme disease agent Borrelia burgdorferi survives in a tick-mouse cycle. In the United States, B. burgdorferi sensu stricto is maintained primarily in Ixodes scapularis ticks, while the European vector of B. burgdorferi sensu stricto, B. garinii, and B. afzelii strains are generally Ixodes ricinus ticks. Feeding of ixodid ticks normally takes several days (2), which gives the host immune system time to react to the arthropod. The ticks have developed several mechanisms to evade both the innate and adaptive host responses, which enable them to take an effective blood meal. Tick saliva possesses proteins with immunosuppressive (14, 18), anticomplement (5,19,27), and antihemostatic (21, 22) activity. Salp15, a feeding-induced tick salivary protein, is known to inhibit CD4 ϩ T-cell activation and proliferation by specifically binding to the CD4 coreceptor of the T cells (1, 6, 13). Also, Salp15 appeared to enhance the survival of B. burgdorferi in the host after transmission by the tick by specifically interacting with B. burgdorferi outer surface protein C (OspC) and providing protection against borreliacidal antibodies (25). Recently we found three Salp15 homologues in I. ricinus ticks (12), and one of these homologues, Salp15 Iric-1, showed 80% similarity to I. scapularis Salp15 (Iscap Salp15) at the DNA level.The innate response, the complement system in particular, plays a crucial role in the eradication of invading pathogens. The complement system is important in the initiation of attack against B. burgdorferi. The spirochetes are opsonized and also directly killed by the formation of the lytic pore-forming membrane attack complex (MAC) (3, 23). B. burgdorferi sensu stricto, B. garinii, and B. afzelii isolates are able to activate complement both by the classical pathway and by the alternative pathway in nonimmune human serum (NHS) in the absence of specific antibodies, but they differ in susceptibility to complement-mediated killing (28). Serum-resistant Borrelia strains are able to evade comple...

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Characterization of the B‐cell inhibitory protein factor in Ixodes ricinus tick saliva: a potential role in enhanced Borrelia burgdoferi transmission

Cited by 67 publications

References 30 publications

Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

Lyme Arthritis: Current Concepts and a Change in Paradigm

The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates

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