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Producer: Aspose.Pdf for .NET 10.1.0; modified using iTextSharp™ 5.4.0 ©2000-2012 1T3XT BVBA (AGPL-version) CreationDate: Mon Nov 12 07:32:03 2018 CET ModDate: Mon Nov 26 09:45:59 2018 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 600.05 x 800 pts Page rot: 0 File size: 870333 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MinionPro-Regular CID Type 0C Identity-H yes no yes 517 0 FAHPJP+MinionPro-It Type 1C Custom yes yes yes 51 0 FAHPKA+Minion-Black Type 1C WinAnsi yes yes no 52 0 FAHPKB+minionblackit Type 1C WinAnsi yes yes no 518 0 FAHPLC+minionblackadditional3 Type 1C WinAnsi yes yes no 519 0 FAHPOB+MinionPro-Regular2 Type 1C Custom yes yes yes 49 0 FAHPOC+MinionMath-Regular Type 1C Custom yes yes yes 50 0 ITDCUU+MinionPro-Regular CID TrueType Identity-H yes yes yes 1 0 FAIAAD+minionmathadditional2 Type 1C Custom yes yes no 53 0 FAIAAE+minionregularadditional Type 1C Custom yes yes no 54 0 FAIACE+MinionMath-Capt Type 1C Custom yes yes yes 100 0 FAIBCP+MinionPro-Bold Type 1C Custom yes yes yes 101 0 FAIBDP+MinionPro-Regular3 Type 1C WinAnsi yes yes no 102 0 FAIBEA+MinionMath-Regular-Graphic Type 1C Custom yes yes yes 103 0 FAIBEB+MinionPro-It2 Type 1C WinAnsi yes yes no 104 0 FAIBGB+MinionPro-Bold2 Type 1C Custom yes yes yes 128 0 FAIBGC+MinionMath-BoldCapt Type 1C Custom yes yes yes 129 0 FAIBGD+MinionMath-Bold Type 1C Custom yes yes yes 130 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-07-07 02:28:19 CEST RepresentationInformation: pmc_30539014.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2019-07-15 03:38:06 CEST Size: 870333 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: ISO PDF/A-1, Level B PDFMetadata: Objects: 587 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Info: Title: Keywords: Creator: Aspose Ltd. 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CIDFontType0: Font: BaseFont: MinionPro-Regular CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: MinionPro-Regular Flags: Nonsymbolic FontBBox: -290, -360, 1684, 989 FontFile3: true CIDFontType2: Font: BaseFont: ITDCUU+MinionPro-Regular CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: ITDCUU+MinionPro-Regular Flags: Nonsymbolic FontBBox: -289, -360, 1684, 917 FontFile2: true XMP: application/pdfCytokine Effect of TLR3, TLR4, and TLR7 Agonists Alone or Associated with Leishmania infantum Antigen on Blood from DogsMartínez-Orellana, PamelaMontserrat-Sangrà, SaraQuirola-Amores, PaulinaGonzález, NoemíSolano-Gallego, LaiaActivation of toll-like receptors (TLRs) has been shown to play an important role in leishmaniosis by enhancing the parasite specific immune responses to control infection. However, the role of TLR agonists has not been studied in detail in dogs. The aim of this study was to determine the effect of TLR3, TLR4, and TLR7 agonists (TLR3a, TLR4a, and TLR7a) alone or in combination with Leishmania infantum antigen (LSA) on TNF-α and IL-6 production in blood from dogs living in endemic areas of canine leishmaniosis (CanL). Twenty-four healthy dogs from Catalonia (n=14) and Ibizan hound dogs from the island of Mallorca (n=10) were enrolled. Whole blood with TLR3a, TLR4a, and TLR7a alone or combined with LSA were cultured separately, and IFN-γ, TNF-α, and IL-6 were measured by ELISA. A significant increase of TNF-α was found for all conditions studied compared to medium alone. Stimulation with TLR4a (p=0.0001) and TLR7a (p=0.005) presented a significantly marked increase in TNF-α and IL-6 production compared to TLR3a. Importantly, significantly higher TNF-α production was found in LSA+TLR4a (p=0.0001) stimulated blood and LSA+TLR7a (p=0.005) compared to LSA alone. All dogs showed higher TNF-α production after LSA+TLR7a compared to TLR7a (p=0.047) and LSA+TLR3a compared to TLR3a (p=0.052). These data indicate a marked inflammatory cytokine effect of TLR4a and TLR7a on blood from healthy dogs living in endemic areas of CanL. Additionally, LSA+TLR7a promoted a synergistic proinflammatory effect with TNF-α in all dogs. Those findings suggest an active role of TLRs in proinflammatory responses, which might be strongly involved in the process of disease resolution.BioMed Research InternationalHindawi2018/11/12Research articledoi:10.1155/2018/5693736en Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 298, 522, 311, 534 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Annotation: Subtype: Link Rect: 90, 138, 94, 149 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Destination: 206 Annotation: Subtype: Link Rect: 226, 127, 232, 137 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Destination: 206 Annotation: Subtype: Link Rect: 152, 93, 158, 103 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Destination: 206 Annotation: Subtype: Link Rect: 162, 93, 167, 103 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Destination: 206 Annotation: Subtype: Link Rect: 418, 193, 424, 203 Flags: Print, NoZoom, NoRotate AppearanceDictionary: true Destination: 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