Proinflammatory Response of Human Trophoblastic Cells to Brucella abortus Infection and upon Interactions with Infected Phagocytes

FERNANDEZ AG; FERRERO MC,; HIELPOS S; FOSSATI CA; BALDI PC

BIOLOGY OF REPRODUCTION

SOC STUDY REPRODUCTION

Lugar: Madison; Año: 2016 vol. 94 p. 1 - 11

0006-3363

Trophoblastsare targets of infection by Brucella spp. but their role in the pathophysiologyof pregnancy complications of brucellosis is unknown. Here we show that Brucellaabortus invades and replicates in the human trophoblastic cell line Swan-71 andthat the intracellular survival of the bacterium depends on a functional virB operon.Theinfection elicited significant increments of interleukin 8 (IL8), monocytechemotactic protein 1 (MCP-1), and IL6 secretion, but levels of IL1beta andtumor necrosis factor-alpha (TNF-alpha) did not vary significantly. Suchproinflammatory response was not modified by the absence of the Brucella TIRdomain-containing proteins BtpA and BtpB. Thestimulation of Swan-71 cells with conditioned medium (CM) from B. abortus-infectedhuman monocytes (THP-1 cells) or macrophages induced a significant increase ofIL8, MCP-1 and IL6 as compared to stimulation with CM from non-infected cells.Similar results were obtained when stimulation was performed with CM frominfected neutrophils. Neutralizationstudies showed that IL1beta and/or TNF-alpha mediated the stimulating effectsof CM from infected phagocytes. Reciprocally, stimulation of monocytes andneutrophils with CM from Brucella-infected trophoblasts increased IL8 and/ orIL6 secretion. Theseresults suggest that human trophoblasts may provide a local inflammatoryenvironment during B. abortus infections either through a direct response tothe pathogen or through interactions with monocytes/macrophages or neutrophils,potentially contributing to the pregnancy complications of brucellosis.