Abstract
Brucella spp. have been associated with abortion in humans and animals. Although the mechanisms involved are not well established, it is known that placental Brucella infection is accompanied by inflammatory phenomena. The ability of Brucella abortus to infect and survive in human endometrial stromal cells (T-HESC cell line) and the cytokine response elicited were evaluated. B. abortus was able to infect and proliferate in both non-decidualized and decidualized T-HESC cells. Intracellular proliferation depended on the expression of a functional virB operon in the pathogen. B. abortus internalization was inhibited by cytochalasin D and to a lower extent by colchicine, but was not affected by monodansylcadaverine. The infection did not induce cytotoxicity and did not alter the decidualization status of cells. B. abortus infection elicited the secretion of IL-8 and MCP-1 in either decidualized or non-decidualized T-HESC, a response also induced by heat-killed B. abortus and outer membrane vesicles derived from this bacterium. The stimulation of T-HESC with conditioned media from Brucella-infected macrophages induced the production of IL-6, MCP-1 and IL-8 in a dose-dependent manner, and this effect was shown to depend on IL-1β and TNF-α. The proinflammatory responses of T-HESC to B. abortus and to factors produced by infected macrophages may contribute to the gestational complications of brucellosis.
Highlights
Human brucellosis, a zoonotic disease mostly caused by Brucella melitensis, B. suis and B. abortus, affects over 500,000 people each year around the world [1]
Brucella abortus Infects and Replicates in Both Decidualized and Non-Decidualized T-HESC Cells. Both decidualized and non-decidualized T-HESC endometrial cells were infected with B. abortus at a multiplicity of infection (MOI) of 250 bacteria/cell, and colony-forming units (CFU) of intracellular bacteria were determined at different times post-infection (p.i.)
To assess the ability of B. abortus to induce a proinflammatory response in T-HESC, these cells were infected with the wild type strain and the btpAbtpB mutant, and the levels of IL-8 and MCP-1 were measured in culture supernatants
Summary
A zoonotic disease mostly caused by Brucella melitensis, B. suis and B. abortus, affects over 500,000 people each year around the world [1]. The infection can be found in several domestic animals (cattle, sheep, goats, pigs, and dogs) and in some wild species. Transmission to humans usually occurs by contact with infected animal tissues and consumption of dairy products. The clinical manifestations of human brucellosis are usually linked to inflammatory phenomena in the affected organs [2]. Involvement with the reproductive organs is common in animals, which frequently present problems such as abortion and perinatal death. Studies performed in animals have shown that placental Brucella infection is accompanied by the infiltration of inflammatory cells [3,4]
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