Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Research Article J Innate Immun 2011;3:623–630 DOI: 10.1159/000328851 Functional Genomics of Tick Thioester-Containing Proteins Reveal the Ancient Origin of the Complement System Veronika Buresova   a Ondrej Hajdusek   a, b Zdenek Franta   a Gabriela Loosova   a Lenka Grunclova   a Elena A. Levashina   b Petr Kopacek   a   a  Institute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, Ceske Budejovice, Czech Republic; b  UPR9022 CNRS, U963 Inserm, Université de Strasbourg, Strasbourg, France plement system. Importantly, understanding the tick im- mune mechanisms should provide new concepts for effi- cient transmission blocking of tick-borne diseases. Copyright © 2011 S. Karger AG, Basel Introduction Ticks are blood-feeding ectoparasites (Chelicerata, Arachnida) and vectors of a variety of pathogens (viruses, bacteria, fungi and protozoa) that pose serious health and socioeconomical problems [1]. Ticks of the genus Ixodes are three-host species, where all stages (larva, nymph and adult female) feed on a different vertebrate host and con- tribute to the pathogen transmission [2]. The feeding is a slow process, taking from a few days (larvae and nymphs) to more than a week in adults. Before the adult female drops off the host, it consumes more than half a milliliter of blood, which accumulates in numerous gut diverticu- lae. The excess of ingested fluid is continuously excreted from the gut by the midgut cells into the hemolymph, re- Key Words Complement  Hemocyte  Ixodes   2 -Macroglobulin  Phagocytosis  RNA interference  Thioester-containing proteins  Tick Abstract Ticks are important ectoparasites and vectors of multiple human and animal diseases. The obligatory hemophagy of ticks provides a formidable route for parasite transmission from one host to another. Parasite survival inside the tick re- lies on the ability of a pathogen to escape or inhibit tick im- mune defenses, but the molecular interactions between the tick and its pathogens remain poorly understood. Here we report that tick genomes are unique in that they contain all known classes of the  2 -macroglobulin family (  2 M-F) pro- teins:  2 -macroglobulin pan-protease inhibitors, C3 com- plement components, and insect thioester-containing and macroglobulin-related proteins. By using RNA interference- mediated gene silencing in the hard tick Ixodes ricinus we demonstrated the central role of a C3-like molecule in the phagocytosis of bacteria and revealed nonredundant func- tions for  2 M-F proteins. Assessment of  2 M-F functions in a single organism should significantly contribute to the gen- eral knowledge on the evolution and function of the com- Received: March 22, 2011 Accepted after revision: April 29, 2011 Published online: July 30, 2011 Journal of Innate Immunity Dr. Petr Kopacek Institute of Parasitology, Biology Centre Academy of Sciences of the Czech Republic, Branisovska 31 CZ–370 05 Ceske Budejovice (Czech Republic) Tel. +420 387 772 207, E-Mail kopajz  @  paru.cas.cz © 2011 S. Karger AG, Basel 1662–811X/11/0036–0623$38.00/0 Accessible online at: www.karger.com/jin V.B. and O.H. contributed equally to this work. Downloaded by: Univ.-Bibliothek Frankfurt 141.2.202.224 - 3/18/2014 10:37:22 AM