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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Tick saliva induces regulatory dendritic cells: MAP-kinases and Toll-like receptor-2 expression as potential targets

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Oliveira, Carlo Jose F. [1] ; Carvalho, Wanessa A. [1] ; Garcia, Gustavo R. [1] ; Gutierrez, Fredy R. S. [1] ; de Miranda Santos, Isabel K. F. [1] ; Silva, Joao S. [1] ; Ferreira, Beatriz R. [2, 1]
Total Authors: 7
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14040902 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Nursing Ribeirao Preto, Dept Maternal Child Nursing & Publ Hlth, BR-14040902 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Veterinary Parasitology; v. 167, n. 2-4, SI, p. 288-297, FEB 10 2010.
Web of Science Citations: 31

Ticks (Acari: Ixodidae) are bloodsucking ectoparasitic arthropods of human and veterinary medical importance. Tick saliva has been shown to contain a wide range of bioactive molecules with vasodilatory, antihemostatic, and immunomodulatory activities. We have previously demonstrated that saliva from Rhipicephalus sanguineus ticks inhibits the maturation of dendritic cells (DCs) stimulated with LPS. Here we examined the mechanism of this immune subversion, evaluating the effect of tick saliva on Toll-like receptor (TLR)-4 signalling pathway in bone marrow-derived DCs. We demonstrated that R. sanguineus tick saliva impairs maturation of DCs stimulated with LIPS, a TLR-4 ligand, leading to increased production of interleukin (IL)-10 and reduced synthesis of IL-12p70 and TNF-alpha. The immunomodulatory effect of the tick saliva on the production of pro-inflammatory cytokines by DCs stimulated with LPS was associated with the observation that tick saliva inhibits the activation of the ERK 1/2 and p38 MAP kinases. These effects were independent of the expression of TLR-4 on the surface of DCs. Additionally, saliva-treated DCs also presented a similar pattern of cytokine modulation in response to other TLR ligands. Since the recent literature reports that several parasites evade immune responses through TLR-2-mediated production of IL-10, we evaluated the effect of tick saliva on the percentage of TLR-2(+) DCs stimulated with the TLR-2 ligand lipoteicoic acid (LTA). The data showed that the population of DCs expressing TLR-2 was significantly increased in DCs treated with LTA plus saliva. In addition, tick saliva alone increased the expression of TLR-2 in a dose- and time-dependent manner. Our data suggest that tick saliva induces regulatory DCs, which secrete IL-10 and low levels of IL-12 and TNF-alpha when stimulated by TLR ligands. Such regulatory DCs are associated with expression of TLR-2 and inhibition of ERK and p38, which promotes the production of IL-10 and thus down-modulates the host's immune response, possibly favouring susceptibility to tick infestations. (C) 2009 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 07/00035-8 - Role of the toll-like receptors (TLRs) on the tick-host interface
Grantee:Beatriz Rossetti Ferreira
Support type: Regular Research Grants