Infection by Brucella melitensis or Brucella papionis modifies essential physiological functions of human trophoblasts

Abstract

Brucellosis is a zoonosis caused by bacteria of the Brucella genus. In ruminants, brucellosis causes abortion, followed by chronic infection and secretion of bacteria in milk. In humans, it usually presents as flu‐like symptoms, with serious complications if untreated. Epidemiological studies have only recently established that brucellosis can also cause pregnancy complications in women, but the pathogenic mechanisms are unknown. Pioneering studies in ruminants showed that Brucella infect trophoblasts and then colonise the placenta where they grow to high density. A recent study showed that the main zoonotic Brucella species can infect human cytotrophoblasts (CTB) and extravillous trophoblasts (EVT). In this work, we show that Brucella papionis (associated with stillbirth in primates) also infects human trophoblasts. However, it replicates actively in CTB, whereas its replication is very restricted within EVT. We also observed alteration of several trophoblastic functions upon infection by B. papionis or Brucella melitensis (the most prevalent species in human brucellosis). Infection altered the production of hormones, the ability of CTB to form syncytiotrophoblasts, and the invasion capacity of EVT. We also found that infection can spread between different types of trophoblasts. These findings constitute a new step in understanding how Brucella infection causes adverse pregnancy outcomes.

Kinetics of Placental Infection by Different Smooth Brucella Strains in Mice

“…Although both B. melitensis strains showed different patterns of intracellular multiplication in BeWo, no cytotoxicity differences were detected between them. In contrast to previous reports [ 35 , 36 ], we were able to detect higher LDH concentration in infected than in non-infected BeWo cells, which is in agreement to those detected by Salcedo and cols. in 16M infected JEG-3 trophoblast cells [ 16 ].…”

“…As in our work, trophoblastic cell lines have demonstrated their suitability for Brucella pathogenesis research [ 15 , 16 , 33 , 34 , 36 , 43 ]. This finding could be attributable to the presence of detectable concentrations of hypothetical factors of Brucella tropism, such as erythritol and aldose reductase [ 4 , 45 ].…”

Brucella ceti sequence type 23, 26, and 27 infections in North American cetaceans

“…Placental infection leading to Brucella pneumonia and sepsis seems most likely in these animals, though placental tissue was not available for examination. The general tropism of Brucella to bovine and human fetal trophoblasts has been observed in terrestrial Brucella species (Sa martino & Enright 1993, García-Méndez et al 2019, and likely a similar pathogenesis exists for cetaceans (González-Barrientos et al 2010, Mackie et al 2020, Hernández-Mora et al 2021. Milk was seldom available for PCR testing, though a female with a positive Brucella PCR on milk lacked evidence of mastitis.…”

The Retrospective on Atypical Brucella Species Leads to Novel Definitions

“…At present, little is known about the interactions with mammalian hosts. Recently, however, as described for the major zoonotic species, B. papionis, associated with stillbirth in primates, proved to infect human trophoblasts, replicating preferentially in cytotrophoblasts and affecting trophoblast functions [156]. Further work will be necessary to extend these studies to other models of infection, comparing the fate of both species with that of classical and other novel Brucella strains.…”