Pathogenic Brucellae Replicate in Human Trophoblasts

Salcedo, Suzana P.; Chevrier, Nicolas; Lacerda, Thaís Lourdes Santos; Amara, Amira Ben; Gerart, Sarah; Arce‐Gorvel, Vilma; Chastellier, Chantal de; Blasco, J.M.; Mège, Jean‐Louis; Gorvel, Jean‐Pierre

doi:10.1093/infdis/jit007

Cited by 65 publications

(67 citation statements)

References 31 publications

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“…By this way, Brucella reproduces within ER-derived compartments in both phagocytes (47,50,52), and in trophoblasts of infected animals (53)(54)(55)(56). A recent study showed that Brucella replicates in several human trophoblast subpopulations and can interfere with the invasive capacity of extravillous trophoblast-like cells (57). This novel replication profiles of Brucella in human trophoblasts give insights into the pathogenesis of infectious abortion (58).…”

Section: Abortionsmentioning

confidence: 99%

The Effect of Brucellosis on Women’s Health and Reproduction

Kurdoğlu¹,

Cetin²,

Kurdoğlu³

et al. 2015

IJWHR

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IntroductionBrucellosis is a zoonotic disease of worldwide distribution which still remains endemic in some developing countries, causing devastating economic losses. Since it is transmissible to humans through direct contact with infected animals, consumption of their milk and dairy products, or inhalation of contaminated aerosols, it is considered a big threat for public health. At this point, the effect of Brucella infection on women's health and reproduction gains an extraordinary importance due to its potential harmful effects on female reproductive system and pregnancy. Therefore, in this report we aimed to review the available literature related to human brucellosis in order to characterize the basic microbiological features as well as the risk factors and clinical presentations of the disease and its complications related to various aspects of reproductive health. Materials and MethodsIn order to look for original articles, review articles, case series, case reports and editorials related to the effects of brucellosis on women's health and reproduction, various internet engines including PubMed, Up To Date, Google, Google Scholar and Cochrane Library were searched between February 2015 and June 2015. Directly or indirectly related information from 75 reports, the earliest reported in 1917 and the latest in 2015 were identified. The words used during the search process were "Brucella," "brucellosis, " "women's health, " "human pregnancy, " "human reproduction, " "abortion, " "preterm birth, " "intrauterine fetal demise, " and "intrauterine fetal death". Results General Features of Brucella Species and InfectionThe main pathogenic species worldwide are Brucella abortus (B. abortus), responsible for bovine brucellosis, Brucella melitensis (B. melitensis), the main etiologic agent of ovine and caprine brucellosis, and Brucella suis (B. suis), which has a wide host range, not being confined to swine (1). B. melitensis is responsible for the majority of human infections and is primarily food-borne. B. abortus and B. suis infections are generally sporadic and Brucella canis infections are the least common in humans and are generally laboratory-acquired (2,3). AbstractDue to its potential harmful effects on the general health and reproductive life of the women, in the light of available literature, it was aimed to review the effect of human brucellosis on women's health and reproduction. Data from 75 reports belonging to the years 1917 through 2015, obtained via a search on various internet sources by the words "Brucella", "brucellosis, " "women's health, " "human pregnancy, " "human reproduction, " "abortion, " "preterm birth, " "intrauterine fetal demise, " and "intrauterine fetal death" were used to characterize basic microbiological features together with the risk factors, clinical presentations and complications of the human brucellosis related to various aspects of reproductive well-being. A high rate of spontaneous abortion was a more consistent finding rather than high rates of preterm delivery and intra...

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Section: Abortionsmentioning

confidence: 99%

The Effect of Brucellosis on Women’s Health and Reproduction

Kurdoğlu¹,

Cetin²,

Kurdoğlu³

et al. 2015

IJWHR

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“…replicate within an intracellular compartment that contains ER resident proteins, the molecular mechanisms by which the pathogen secures this replicative niche remain obscure (Qin et al 2008). Brucella replicate in a vacuole derived from the ER in epithelial cells, macrophages, and dendritic cells (Salcedo et al 2013). Thus far, factors that mediate Brucella infection of host cells remain obscure.…”

Section: Introductionmentioning

confidence: 99%

Brucella suis vaccine strain S2-infected immortalized caprine endometrial epithelial cell lines induce non-apoptotic ER-stress

Wang

Lin

Yin

et al. 2015

Cell Stress and Chaperones

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Brucella, which is regarded as an intracellular pathogen responsible for a zoonotic disease called brucellosis, survives and proliferates within several types of phagocytic and non-phagocytic cells. Brucella infects not only their preferred hosts but also other domestic and wild animal species, inducing abortion and infertility. Therefore, the interaction between uterine cells and Brucella is important for understanding the pathogenesis of this disease. In this study, we describe the Brucella suis vaccine strain S2 (B.suis.S2) infection and replication in the immortalized caprine endometrial epithelial cell line hTERT-EECs and the induced cellular and molecular response modulation in vitro. We found that B.suis S2 was able to infect and replicate to high titers and inhibit the proliferation of EECs and induce non-apoptotic pathways, as determined by B.suis.S2 detection using MTT and acridine orange/ethidium bromide (AO/EB) staining and flow cytometry. We explored the evidence of non-apoptotic pathways using real-time quantitative RT-PCR and by western blot analysis. Finally, we discovered the over-expression of GRP78, ATF4, ATF6, PERK, eIF2α, CHOP, and cytochrome c (Cyt-c) but not IRE1, xbp-1, and caspase-3 in B.suis.S2 (HK)-attacked and B.suis.S2-infected cells, suggesting that the molecular mechanism of ER stress sensor activation by B.suis.S2 is basically concomitant with that by B.suis.S2 (HK) and that ER stress, especially the PERK pathway, plays an important role in the process of B.suis.S2 infecting EEC, which may, in part, explain the role of the uterus in the pathogenesis of B.suis.S2.

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“…A recent study has demonstrated that Brucella replicates in several human trophoblast subpopulations and can interfere with the invasive capacity of extravillous trophoblast-like cells in vitro (7). In one of the largest series of pregnancies complicated with brucellosis, we have also showed that brucellosis in pregnancy is associated with increased incidence of spontaneous abortions not only in livestock but also in human pregnancies (8).…”

mentioning

confidence: 54%

What is the Role of Laminin Receptor 1 in Human Reproduction?

Kurdoğlu¹,

Kurdoğlu²

2015

IJWHR

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Dear Editor,The accumulated data related to the recently discovered functions of laminin receptor 1 (LR1) in the early stages of placentation (1-5) made us to think that it may also have an important role in human reproduction, which may be regarded as a very new job for this multifunctional protein overexpressed in many types of cancer and is very well known for its important roles in tumour-cell migration and invasion. In human reproductive physiology, one of the essential steps for the development of a normal pregnancy is the invasion of uterine decidua and myometrium by fetally derived extravillous trophoblast cells and the associated spiral artery transformation which proceed in a complex but stereotyped manner (6). Within this process, laminins which are a family of well-described extracellular matrix glycoproteins have many effects on cell adhesion, differentiation, migration, signalling and invasion. One of the molecules that may also play a key role in both normal and pathologic trophoblast invasion is a non-integrin-type receptor of laminins, laminin receptor 1 (LR1) which acts as a cell-surface receptor of laminin in the interactions for these biological processes. Together with Nagymanyoki et al. (4) we have previously shown LR1 in the decidua of normal and molar human pregnancies (1). Based on the pathological data, there is a growing body of evidence that impaired early trophoblastic invasion and more consistently, restricted endovascular invasion may be associated with preeclampsia which is an almost exclusively human pregnancy-specific syndrome characterized by new-onset proteinuria and hypertension occurring usually after 20 weeks of gestation. For the first time in the literature, we showed that decreased LR1 expression may be related to the shallow trophoblastic invasion in human placentas from preeclamptic patients (2). In the following studies, it has been suggested that knockdown of LR1 may inhibit trophoblast cell invasion and migration by modulating matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) expression via the ERK (extracellular signal-regulated kinases) pathway (5). A recent study has demonstrated that Brucella replicates in several human trophoblast subpopulations and can interfere with the invasive capacity of extravillous trophoblast-like cells in vitro (7). In one of the largest series of pregnancies complicated with brucellosis, we have also showed that brucellosis in pregnancy is associated with increased incidence of spontaneous abortions not only in livestock but also in human pregnancies (8). At this point, we hypothesised that LR1 may also have a role in diminished invasive capacity of extravillous trophoblast-like cells in abortions related to Brucella infections (3). Although it has been suggested that failed trophoblast invasion and spiral artery transformation do not have a pivotal role in the pathogenesis of early miscarriage (6), the abortions related to Brucella infections may be exceptional. As a conclusion, limited present data related to...

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Pathogenic Brucellae Replicate in Human Trophoblasts

Cited by 65 publications

References 31 publications

The Effect of Brucellosis on Women’s Health and Reproduction

The Effect of Brucellosis on Women’s Health and Reproduction

Brucella suis vaccine strain S2-infected immortalized caprine endometrial epithelial cell lines induce non-apoptotic ER-stress

What is the Role of Laminin Receptor 1 in Human Reproduction?

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