Immune Responses Potentially Involved in the Gestational Complications of Brucella Infection

Abstract

Infection by Brucella species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring. The pathogen has a marked tropism for the placenta and the pregnant uterus and has the ability to invade and replicate within cells of the maternal-fetal unit, including trophoblasts and decidual cells. Placentitis is a common finding in infected pregnant animals. Several proinflammatory factors have been found to be increased in both the placenta of Brucella-infected animals and in trophoblasts or decidual cells infected in vitro. As normal pregnancies require an anti-inflammatory placental environment during most of the gestational period, Brucella-induced placentitis is thought to be associated with the obstetric complications of brucellosis. A few studies suggest that the blockade of proinflammatory factors may prevent abortion in these cases.

Keywords: Brucella; abortion; decidua; endometrial cells; inflammation; intracellular replication; placentitis; trophoblasts; vertical transmission.

Figure 1

Brucella interaction with placental cells in different host species and the resulting inflammatory response. The morphological and histological classification of placentation in different hosts or infection models is depicted. Proinflammatory responses to Brucella have been described in the different hosts, although immune responses have been described in greater detail for human lines and the murine model. Cross-talk between trophoblasts and phagocytes takes place during placental infections by Brucella, leading to increased levels of proinflammatory cytokines. Infected placental trophoblasts secrete HMGB1, IL-8, MCP-1, GM-CSF, and IL-6, which could attract and activate decidual macrophages, monocytes, and PMN to the site of infection. Infected monocytes and PMN produce high levels of IL-8, IL-6, MCP-1, TNF-α, and IL-1 β that potentiate EVT proinflammatory response. The pro-inflammatory environment impacts progesterone production, which results in increased IFN-γ and IL-6 production. Altogether, this inflammatory environment may contribute to the gestational complications of brucellosis. EVT: Extravillous Trophoblast; CTB: Cytotrophoblast; dSC: decidualized Stromal Cell; PMN: Polymorphonuclear cell; dPMN: decidual Polymorphonuclear cell; P4: Progesterone.