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A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06420, USA.
Cell host & microbe (Impact Factor: 12.19). 08/2011; 10(2):136-46. DOI: 10.1016/j.chom.2011.06.010
Source: PubMed

ABSTRACT The Lyme disease agent Borrelia burgdorferi is primarily transmitted to vertebrates by Ixodes ticks. The classical and alternative complement pathways are important in Borrelia eradication by the vertebrate host. We recently identified a tick salivary protein, designated P8, which reduced complement-mediated killing of Borrelia. We now discover that P8 interferes with the human lectin complement cascade, resulting in impaired neutrophil phagocytosis and chemotaxis and diminished Borrelia lysis. Therefore, P8 was renamed the tick salivary lectin pathway inhibitor (TSLPI). TSLPI-silenced ticks, or ticks exposed to TSLPI-immune mice, were hampered in Borrelia transmission. Moreover, Borrelia acquisition and persistence in tick midguts was impaired in ticks feeding on TSLPI-immunized, B. burgdorferi-infected mice. Together, our findings suggest an essential role for the lectin complement cascade in Borrelia eradication and demonstrate how a vector-borne pathogen co-opts a vector protein to facilitate early mammalian infection and vector colonization.

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Available from: Jianfeng Dai, Jan 21, 2014
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    • "I. scapularis and I. ricinus saliva inhibit alternative pathway C3 convertase activity by causing dissociation of C3b from Bb (Valenzuela et al., 2000; Daix et al., 2007; Tyson et al., 2007). Tick salivary lectin pathway inhibitor (TSPLI) present in saliva of I. scapularis reduces spirochete killing by inhibiting lectin pathway complement mediated activation on the surface of B. burgdorferi (Schuijt et al., 2011). In concert with tick modulation of host complement defenses, B. burgdorferi itself inhibits innate immune defenses, including complement activation (Singh and Girschick, 2004; Hovius, 2009). "
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    • "For instance, ISAC, Salp20, IRAC I/II, TSLP1, and Salp15 inhibit complement through different mechanisms. ISAC, Salp20, and IRACI/II dissociate the crucial complement convertase molecule C3 (Paesen et al., 1999; Lögdberg and Wester, 2000; Valenzuela et al., 2000; Anguita et al., 2002; Leboulle et al., 2002; Sangamnatdej et al., 2002; Andersen et al., 2005; Garg et al., 2006; Daix et al., 2007; Schroeder et al., 2007; Tyson et al., 2007, 2008; Déruaz et al., 2008; Schuijt et al., 2011). However, TSLP1 and Salp15 target the complement pathway by inhibiting mannosebinding lectin and MAC, respectively (Schuijt et al., 2008). "
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