Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
- MeSH
- Anaplasma phagocytophilum patogenita MeSH
- bakteriální infekce imunologie metabolismus MeSH
- buněčné linie MeSH
- členovci metabolismus mikrobiologie fyziologie MeSH
- Dermacentor metabolismus mikrobiologie fyziologie MeSH
- extracelulární vezikuly metabolismus ultrastruktura MeSH
- Francisella tularensis patogenita MeSH
- genová ontologie MeSH
- intravitální mikroskopie MeSH
- klíšťata metabolismus mikrobiologie MeSH
- klíště metabolismus mikrobiologie fyziologie MeSH
- kůže imunologie mikrobiologie parazitologie MeSH
- lidé MeSH
- membránový protein 2 asociovaný s vezikuly metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- proteiny R-SNARE metabolismus MeSH
- proteomika MeSH
- T-lymfocyty metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- transmisní elektronová mikroskopie MeSH
- zánět imunologie metabolismus parazitologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- membránový protein 2 asociovaný s vezikuly MeSH
- proteiny R-SNARE MeSH
BACKGROUND: Tick carrier proteins are able to bind, transport, and store host-blood heme, and thus they function also as antioxidants. Nevertheless, the role of carrier proteins in ticks is not fully understood. Some of them are found also in tick males which do not feed on hosts to such an extent such as females (there are differences in male feeding in different tick species) and thus they are not dealing with such an excess of heme; some of the carrier proteins were found in salivary glands where the processing of blood and thus release of heme does not occur. Besides, the carrier proteins bind relatively low amounts of heme (in one case only two molecules of heme per protein) compared to their sizes (above 200 kDa). The main aim of this study is the biochemical characterization of a carrier protein from the ornate sheep tick Dermacentor marginatus, hemelipoglycoprotein, with emphasis on its size in native conditions, its glycosylation and identification of its modifying glycans, and examining its carbohydrate-binding specificity. RESULTS: Hemelipoglycoprotein from D. marginatus plasma was purified in native state by immunoprecipitation and denatured using electroelution from SDS-PAGE separated plasma. The protein (290 kDa) contains two subunits with molecular weights 100 and 95 kDa. It is glycosylated by high-mannose and complex N-glycans HexNAc(2)Hex(9), HexNAc(2)Hex(10), HexNAc(4)Hex(7), and HexNAc(4)Hex(8). The purified protein is able to agglutinate red blood cells and has galactose- and mannose-binding specificity. The protein is recognized by antibodies directed against plasma proteins with hemagglutination activity and against fibrinogen-related lectin Dorin M from the tick Ornithodoros moubata. It forms high-molecular weight complexes with putative fibrinogen-related proteins and other unknown proteins under native conditions in tick plasma. Feeding does not increase its amounts in male plasma. The hemelipoglycoprotein was detected also in hemocytes, salivary glands, and gut. In salivary glands, the protein was present in both glycosylated and nonglycosylated forms. CONCLUSION: A 290 kDa hemelipoglycoprotein from the tick Dermacentor marginatus, was characterized. The protein has two subunits with 95 and 100 kDa, and bears high-mannose and complex N-linked glycans. In hemolymph, it is present in complexes with putative fibrinogen-related proteins. This, together with its carbohydrate-binding activity, suggests its possible involvement in tick innate immunity. In fed female salivary glands, it was found also in a form corresponding to the deglycosylated protein.
- MeSH
- Dermacentor chemie metabolismus MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- glykoproteiny chemie izolace a purifikace metabolismus MeSH
- glykosylace MeSH
- hemaglutininy chemie izolace a purifikace metabolismus MeSH
- hemoproteiny chemie izolace a purifikace metabolismus MeSH
- imunoprecipitace MeSH
- lipoproteiny chemie izolace a purifikace metabolismus MeSH
- metabolismus sacharidů MeSH
- molekulová hmotnost MeSH
- Ornithodoros imunologie MeSH
- ovce MeSH
- podjednotky proteinů chemie izolace a purifikace metabolismus MeSH
- protilátky imunologie MeSH
- transportní proteiny chemie izolace a purifikace metabolismus MeSH
- vazba proteinů MeSH
- zkřížené reakce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- glykoproteiny MeSH
- hemaglutininy MeSH
- hemoproteiny MeSH
- lipoproteiny MeSH
- podjednotky proteinů MeSH
- protilátky MeSH
- transportní proteiny MeSH