AUTHOR=Esteves Eliane , Bizzarro Bruna , Costa Francisco Borges , Ramírez-Hernández Alejandro , Peti Ana Paula Ferranti , Cataneo Allan Henrique Depieri , Wowk Pryscilla Fanini , Timóteo Rodolfo Pessato , Labruna Marcelo Bahia , Silva Junior Pedro Ismael , Silva Célio Lopes , Faccioli Lúcia Helena , Fogaça Andréa Cristina , Sorgi Carlos Arterio , Sá-Nunes Anderson 

TITLE=Amblyomma sculptum Salivary PGE2 Modulates the Dendritic Cell-Rickettsia rickettsii Interactions in vitro and in vivo

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00118

DOI=10.3389/fimmu.2019.00118

ISSN=1664-3224

ABSTRACT=<p><italic>Amblyomma sculptum</italic> is an important vector of <italic>Rickettsia rickettsii</italic>, causative agent of Rocky Mountain spotted fever and the most lethal tick-borne pathogen affecting humans. To feed on the vertebrate host's blood, <italic>A. sculptum</italic> 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 <italic>A. sculptum</italic> saliva-host DC network and the biochemical nature of the immunomodulatory component(s) involved in this interface. <italic>A. sculptum</italic> 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<sub>2</sub> (PGE<sub>2</sub>) 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 <italic>R. rickettsii</italic> was demonstrated for the first time leading to proinflammatory cytokine production that was inhibited by both <italic>A. sculptum</italic> saliva and PGE<sub>2</sub>, a result also achieved with human DCs. The adoptive transfer of murine DCs incubated with <italic>R. rickettsii</italic> followed by treatment with <italic>A. sculptum</italic> saliva or PGE<sub>2</sub> 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<sub>2</sub> as a universal immunomodulator of tick saliva. In addition, it contributes to new approaches to explore <italic>R. rickettsii</italic>-DC interactions both <italic>in vitro</italic> and <italic>in vivo</italic>.</p>