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Novel Immunomodulators from Hard Ticks Selectively Reprogramme Human Dendritic Cell Responses

SYSNO ASEP	0397469
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Novel Immunomodulators from Hard Ticks Selectively Reprogramme Human Dendritic Cell Responses
Tvůrce(i)	Preston, S. G. (GB) Majtán, J. (SK) Kouremenou, C. (GB) Rysnik, O. (GB) Burger, L.F. (GB) Cabezas Cruz, Alejandro (BC-A) Guzman, M.C. (CU) Nunn, M. A. (GB) Paesen, G.C. (GB) Nuttall, P.A. (GB) Austyn, J.M. (GB)
Zdroj.dok.	PLoS Pathogens. - : Public Library of Science - ISSN 1553-7366 Roč. 9, č. 6 (2013), e1003450
Poč.str.	18 s.
Forma vydání	Online - E
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	scapularis salivary protein ; histamine-binding proteins ; tumor necrosis factor
Vědní obor RIV	EC - Imunologie
Institucionální podpora	BC-A - RVO:60077344
UT WOS	000321206600049
DOI	10.1371/journal.ppat.1003450
Anotace	Hard ticks subvert the immune responses of their vertebrate hosts in order to feed for much longer periods than other blood-feeding ectoparasites; this may be one reason why they transmit perhaps the greatest diversity of pathogens of any arthropod vector. Tick-induced immunomodulation is mediated by salivary components, some of which neutralise elements of innate immunity or inhibit the development of adaptive immunity. As dendritic cells (DC) trigger and help to regulate adaptive immunity, they are an ideal target for immunomodulation. However, previously described immunoactive components of tick saliva are either highly promiscuous in their cellular and molecular targets or have limited effects on DC. Here we address the question of whether the largest and globally most important group of ticks (the ixodid metastriates) produce salivary molecules that specifically modulate DC activity. We used chromatography to isolate a salivary gland protein (Japanin) from Rhipicephalus appendiculatus ticks. Japanin was cloned, and recombinant protein was produced in a baculoviral expression system. We found that Japanin specifically reprogrammes DC responses to a wide variety of stimuli in vitro, radically altering their expression of co-stimulatory and co-inhibitory transmembrane molecules (measured by flow cytometry) and their secretion of pro-inflammatory, anti-inflammatory and T cell polarising cytokines (assessed by Luminex multiplex assays); it also inhibits the differentiation of DC from monocytes. Sequence alignments and enzymatic deglycosylation revealed Japanin to be a 17.7 kDa, N-glycosylated lipocalin. Using molecular cloning and database searches, we have identified a group of homologous proteins in R. appendiculatus and related species, three of which we have expressed and shown to possess DC-modulatory activity. All data were obtained using DC generated from at least four human blood donors, with rigorous statistical analysis.
Pracoviště	Biologické centrum (od r. 2006)
Kontakt	Dana Hypšová, eje@eje.cz, Tel.: 387 775 214
Rok sběru	2014

Počet záznamů: 1