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Amblyomma sculptum Salivary PGE(2) Modulates the Dendritic Cell-Rickettsia rickettsii Interactions in vitro and in vivo

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Esteves, Eliane [1] ; Bizzarro, Bruna [1] ; Costa, Francisco Borges [2] ; Ramirez-Hernandez, Alejandro [2] ; Ferranti Peti, Ana Paula [3] ; Depieri Cataneo, Allan Henrique [4] ; Wowk, Pryscilla Fanini [4] ; Timoteo, Rodolfo Pessato [5] ; Labruna, Marcelo Bahia [2] ; Silva Junior, Pedro Ismael [6] ; Silva, Celio Lopes [7] ; Faccioli, Lucia Helena [3] ; Fogaca, Andrea Cristina [8, 9] ; Sorgi, Carlos Arterio [3] ; Sa-Nunes, Anderson [1, 9]
Número total de Autores: 15
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Prevent Vet Med & Anim Hlth, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil
[4] Fundacao Oswaldo Cruz, Carlos Chagas Inst, Lab Mol Virol, Curitiba, Parana - Brazil
[5] Univ Fed Triangulo Mineiro, Inst Nat & Biol Sci, Uberaba - Brazil
[6] Butantan Inst, Special Lab Appl Toxinol, Sao Paulo - Brazil
[7] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[8] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil
[9] Natl Council Sci & Technol Dev INCT CNPq, Natl Inst Sci & Technol Mol Entomol, Rio De Janeiro - Brazil
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 10, FEB 4 2019.
Citações Web of Science: 0

Amblyomma sculptum is an important vector of Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever and the most lethal tick-borne pathogen affecting humans. To feed on the vertebrate host's blood, A. sculptum secretes a salivary mixture, which may interact with skin resident dendritic cells (DCs) and modulate their function. The present work was aimed at depicting the A. sculptum saliva-host DC network and the biochemical nature of the immunomodulatory component(s) involved in this interface. A. sculptum saliva inhibits the production of inflammatory cytokines by murine DCs stimulated with LPS. The fractionation of the low molecular weight salivary content by reversed-phase chromatography revealed active fractions eluting from 49 to 55% of the acetonitrile gradient. Previous studies suggested that this pattern of elution matches with that observed for prostaglandin E-2 (PGE(2)) and the molecular identity of this lipid mediator was unambiguously confirmed by a new high-resolution mass spectrometry methodology. A productive infection of murine DCs by R. rickettsii was demonstrated for the first time leading to proinflammatory cytokine production that was inhibited by both A. sculptum saliva and PGE(2), a result also achieved with human DCs. The adoptive transfer of murine DCs incubated with R. rickettsii followed by treatment with A. sculptum saliva or PGE(2) did not change the cytokine profile associated to cellular recall responses while IgG2a-specific antibodies were decreased in the serum of these mice. Together, these findings emphasize the role of PGE(2) as a universal immunomodulator of tick saliva. In addition, it contributes to new approaches to explore R. rickettsii-DC interactions both in vitro and in vivo. (AU)

Processo FAPESP: 15/00658-1 - Novos aspectos funcionais dos eicosanóides
Beneficiário:Lúcia Helena Faccioli
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 13/26450-2 - Caracterização molecular das interações entre carrapatos, riquétsias e hospedeiros vertebrados
Beneficiário:Sirlei Daffre
Linha de fomento: Auxílio à Pesquisa - Temático