Article

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: 12.33). 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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    • "dsRNAinjected ticks were allowed to feed until repletion and weighed to assess feeding efficiency, and guts and salivary glands were dissected for messenger RNA (mRNA) isolation and quantitative RT-PCR as described above. B. burgdorferi burden in mice was assessed by quantitative PCR as described earlier[9]. "
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    • "An indirect assay to measure complement-mediated killing was also employed, adapted from the method described by Kraiczy et al. (2000) and described previously (Schuijt et al., 2011; Wagemakers et al., 2014). A 1.5 × 10 7 spirochaetes of each isolate including the serum sensitive control isolate, A87S, were incubated with NHS or HIS in BSK-II medium with 240 ␮g/ml phenol red (Merck, Darmstadt , Germany) at 33 • C for 10 days. "
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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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