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 relies on the ability of a pathogen to escape or inhibit tick immune 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 α(2)-macroglobulin family (α(2)M-F) proteins: α(2)-macroglobulin pan-protease inhibitors, C3 complement 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 functions for α(2)M-F proteins. Assessment of α(2)M-F functions in a single organism should significantly contribute to the general knowledge on the evolution and function of the complement system. Importantly, understanding the tick immune mechanisms should provide new concepts for efficient transmission blocking of tick-borne diseases.

• MeSH
• alfa-makroglobuliny genetika   MeSH
• Chryseobacterium imunologie   patogenita   MeSH
• fagocytóza genetika   MeSH
• genom imunologie   MeSH
• genomika MeSH
• hemocyty imunologie   metabolismus   mikrobiologie   patologie   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• infekce bakteriemi čeledi Flavobacteriaceae genetika   imunologie   MeSH
• komplement C3 genetika   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• molekulární evoluce MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa-makroglobuliny MeSH
• hmyzí proteiny MeSH
• komplement C3 MeSH
• malá interferující RNA MeSH

The universal protease inhibitors of the alpha(2)-macroglobulin (alpha(2)M) family are evolutionarily conserved constituents of innate immunity, presumably because they guard organisms against undesired proteolytic attacks of a different origin. Here, we determined the primary structure of alpha(2)-macroglobulin from the hard tick Ixodes ricinus (IrAM) by sequencing of overlapping PCR products. Predicted disulfide and glycosylation patterns, post-translational cleavage and alternative splicing within its 'bait region' demonstrate that IrAM is closely related to the alpha(2)-macroglobulin from the soft tick Ornithodoros moubata. The IrAM message is expressed in all tick developmental stages and tissues, except for the gut, and the protein was detected to be mainly present in the hemolymph. Silencing of IrAM by dsRNA interference markedly reduced the phagocytosis of a potential pathogen, Chryseobacterium indologenes, by tick hemocytes both in vitro and in vivo. In contrast, phagocytosis of the Lyme disease spirochete Borrelia burgdorferi or a commensal bacteria Staphylococcus xylosus was not affected by the IrAM knock-down. Similar results were obtained upon deactivation of all thioester proteins in tick hemolymph by methylamine. We have further demonstrated that phagocytosis of C. indologenes is dependent on an active metalloprotease secreted by the bacteria. These data indicate that interaction of tick alpha(2)-macroglobulin with a protease of an invading pathogen is linked with cellular immune response.

• MeSH
• alfa-makroglobuliny chemie   genetika   imunologie   farmakologie   MeSH
• Chryseobacterium imunologie   MeSH
• fagocytóza imunologie   MeSH
• fenantroliny farmakologie   MeSH
• hemocyty účinky léků   imunologie   mikrobiologie   MeSH
• hemolymfa imunologie   MeSH
• klíště genetika   imunologie   mikrobiologie   MeSH
• metaloproteasy účinky léků   metabolismus   MeSH
• methylaminy farmakologie   MeSH
• molekulární sekvence - údaje MeSH
• RNA interference MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,10-phenanthroline MeSH Prohlížeč
• alfa-makroglobuliny MeSH
• fenantroliny MeSH
• metaloproteasy MeSH
• methylamine MeSH Prohlížeč
• methylaminy MeSH