*Brucella abortus* **Proliferates in Decidualized and Non-Decidualized Human Endometrial Cells Inducing a Proinflammatory Response**

**Lucía Zavattieri 1,2,**†**, Mariana C. Ferrero 1,2,**†**, Iván M. Alonso Paiva 1,2, Agustina D. Sotelo 1,2, Andrea M. Canellada 1,2 and Pablo C. Baldi 1,2,\***


Received: 22 March 2020; Accepted: 17 April 2020; Published: 12 May 2020

**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-<sup>α</sup>. The proinflammatory responses of T-HESC to *B. abortus* and to factors produced by infected macrophages may contribute to the gestational complications of brucellosis.

**Keywords:** *Brucella abortus*; human endometrial cells; internalization; intracellular replication; decidualization; chemokines; macrophages
