<i>Ixodes</i> ticks belonging to the <i>Ixodes ricinus</i> complex encode a family of anticomplement proteins

Daix, Virginie; Schroeder, Hélène; Praet, Nicolas; Georgin, J. P.; Chiappino, I.; Gillet, Laurent; Fays, Katalin de; Decrem, Yves; Leboulle, Gérard; Godfroid, Edmond; Bollen, Alex; Pastoret, Paul-Pierre; Gern, Lise; Sharp, Paul M.; Vanderplasschen, Alain

doi:10.1111/j.1365-2583.2006.00710.x

Cited by 82 publications

(75 citation statements)

References 40 publications

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“…None of these showed any functional domains, GO terms or link to a biological pathway, but their high similarity with anti-complement proteins of ixodid ticks (82–100%) suggested anti-complement activity. Such activity has been already identified in I. ricinus SG extracts [29] and some anti-complement proteins have been shown to be up-regulated during blood feeding [30]. In our study, we found that those isotigs annotated as anti-complement proteins were down-regulated in response to B. henselae infection.…”

Section: Anti-complement Proteins Familysupporting

confidence: 75%

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

et al. 2014

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Ixodes ricinus is the most widespread and abundant tick in Europe, frequently bites humans, and is the vector of several pathogens including those responsible for Lyme disease, Tick-Borne Encephalitis, anaplasmosis, babesiosis and bartonellosis. These tick-borne pathogens are transmitted to vertebrate hosts via tick saliva during blood feeding, and tick salivary gland (SG) factors are likely implicated in transmission. In order to identify such tick factors, we characterized the transcriptome of female I. ricinus SGs using next generation sequencing techniques, and compared transcriptomes between Bartonella henselae-infected and non-infected ticks. High-throughput sequencing of I. ricinus SG transcriptomes led to the generation of 24,539 isotigs. Among them, 829 and 517 transcripts were either significantly up- or down-regulated respectively, in response to bacterial infection. Searches based on sequence identity showed that among the differentially expressed transcripts, 161 transcripts corresponded to nine groups of previously annotated tick SG gene families, while the others corresponded to genes of unknown function. Expression patterns of five selected genes belonging to the BPTI/Kunitz family of serine protease inhibitors, the tick salivary peptide group 1 protein, the salp15 super-family, and the arthropod defensin family, were validated by qRT-PCR. IrSPI, a member of the BPTI/Kunitz family of serine protease inhibitors, showed the highest up-regulation in SGs in response to Bartonella infection. IrSPI silencing impaired tick feeding, as well as resulted in reduced bacterial load in tick SGs. This study provides a comprehensive analysis of I. ricinus SG transcriptome and contributes significant genomic information about this important disease vector. This in-depth knowledge will enable a better understanding of the molecular interactions between ticks and tick-borne pathogens, and identifies IrSPI, a candidate to study now in detail to estimate its potentialities as vaccine against the ticks and the pathogens they transmit.

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Section: Anti-complement Proteins Familysupporting

confidence: 75%

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

et al. 2014

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“…Salp20 is a member of the ILP family, containing at least 49 members (7,8,10,11). In addition to Salp20, several members of this family, specifically Isac, Irac I, Irac II, S20Lclone 12, and S20Lclone 2, inhibit the alternative pathway by decay acceleration of the C3 convertase (9 -11) (data not shown).…”

Section: Discussionmentioning

confidence: 97%

“…One property of tick saliva is inhibition of the alternative complement pathway (4 -6). Ixodes scapularis anti-complement protein (Isac) 3 and salivary protein 20 (Salp20), and Ixodes ricinus anti-complement proteins I and II (Irac I and Irac II) are members of a large family of homologous proteins, referred to as the Isac-like protein (ILP) family, that specifically inhibit the alternative pathway by dissociating the components of the C3 convertase, C3b, and cleaved factor B (Bb) (7)(8)(9)(10)(11). While preventing the activation of the alternative pathway, Salp20 also protects Borrelia garinii from complement-mediated killing by normal human serum (NHS) (10), suggesting these anti-complement proteins facilitate tick feeding as well as pathogen transmission and survival.…”

mentioning

confidence: 99%

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

Tyson

Elkins

Silva

2008

The Journal of Immunology

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Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes scapularis anti-complement protein-like family of tick salivary proteins that inhibit the alternative complement pathway. In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, stabilizing the molecule. Salp20 directly bound to and displaced properdin from the C3 convertase. Displacement of properdin accelerated the decay of the C3 convertase, leading to inhibition of the alternative pathway. S20NS is distinct from known decay accelerating factors, such as decay accelerating factor, complement receptor 1, and factor H, which directly interact with either C3b or cleaved factor B.

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“…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. This is the first description of a microorganism binding from the vector a protein that protects the pathogen against the complement system (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

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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Ixodes ticks belonging to the Ixodes ricinus complex encode a family of anticomplement proteins

Cited by 82 publications

References 40 publications

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

IrSPI, a Tick Serine Protease Inhibitor Involved in Tick Feeding and Bartonella henselae Infection

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

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

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