Deconstructing Tick Saliva NON-PROTEIN MOLECULES WITH POTENT IMMUNOMODULATORY PROPERTIES

Autor(es)

Oliveira, Carlo Jose F. ^[1] ; Sa-Nunes, Anderson ^[2] ; Francischetti, Ivo M. B. ^[3] ; Carregaro, Vanessa ^[1] ; Anatriello, Elen ^[1] ; Silva, Joao S. ^[1] ; de Miranda Santos, Isabel K. F. ^[1] ; Ribeiro, Jose M. C. ^[3] ; Ferreira, Beatriz R. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo - Brazil

^[3] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 - USA

^[4] Univ Sao Paulo, Sch Nursing Ribeirao Preto, Dept Maternal Child Nursing & Publ Hlth, BR-14040902 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biological Chemistry; v. 286, n. 13, p. 10960-10969, APR 1 2011.
• Citações Web of Science: 69

Resumo

Dendritic cells (DCs) are powerful initiators of innate and adaptive immune responses. Ticks are blood-sucking ectoparasite arthropods that suppress host immunity by secreting immunomodulatory molecules in their saliva. Here, compounds present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on DC differentiation, cytokine production, and costimulatory molecule expression were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-alpha while potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible for these effects, we fractionated the saliva through microcon filtration and reversed-phase HPLC and tested each fraction for DC maturation. Fractions with proven effects were analyzed by micro-HPLC tandem mass spectrometry or competition ELISA. Thus, we identified for the first time in tick saliva the purine nucleoside adenosine (concentration of similar to 110pmol/mu l) as a potent anti-inflammatory salivary inhibitor of DC cytokine production. We also found prostaglandin E-2 (PGE(2) similar to 100 nM) with comparable effects in modulating cytokine production by DCs. Both Ado and PGE(2) inhibited cytokine production by inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE(2) were able to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis revealed that PGE(2), but not Ado, is the differentiation inhibitor of bone marrow-derived DCs. The presence of non-protein molecules adenosine and PGE(2) in tick saliva indicates an important evolutionary mechanism used by ticks to subvert host immune cells and allow them to successfully complete their blood meal and life cycle. (AU)

• Processo FAPESP: 07/00035-8 - Papel dos receptores toll-like (TLRs) na interface carrapato-hospedeiro
• Beneficiário: Beatriz Rossetti Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/54985-4 - Efeito da saliva de carrapatos Rhipicephalus sanguineus sobre a expressão e ativação de receptores toll-like (TLRs)
• Beneficiário: Carlo José Freire de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado