Interferon-γ promotes abortion due to Brucella infection in pregnant mice

Department of Applied Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
BMC Microbiology (Impact Factor: 2.73). 02/2005; 5:22. DOI: 10.1186/1471-2180-5-22
Source: PubMed


The mechanisms of abortion induced by bacterial infection are largely unknown. In the present study, we investigated abortion induced by Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in a mouse model.
High rates of abortion were observed for bacterial infection on day 4.5 of gestation, but not for other days. Regardless of whether fetuses were aborted or stayed alive, the transmission of bacteria into the fetus and bacterial replication in the placenta were observed. There was a higher degree of bacterial colonization in the placenta than in other organs and many bacteria were detected in trophoblast giant cells in the placenta. Intracellular growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce abortion. In the case of abortion, around day 7.5 of gestation (period of placental development), transient induction of IFN-gamma production was observed for infection by the wild type strain, but not by the virB4 mutant and S19. Neutralization of IFN-gamma, whose production was induced by infection with B. abortus, served to prevent abortion.
These results indicate that abortion induced by B. abortus infection is a result of transient IFN-gamma production during the period of placental development.

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    • "Ba is thought to be transmitted in cows via the oro-pharyngeal route after exposure to infected placenta released on abortion. It colonizes placenta in its natural hosts (Carvalho Neta et al. 2010) as well as giant trophoblasts in a mouse animal model (Tobias et al. 1993; Kim et al. 2005b). It could be transmitted to the fetus, indicating a crossing of the placental barrier. "
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    • "Cytokines can cause either harmful or beneficial outcomes in pregnancy, for example, an overproduction of interferon γ and TNF- may be associated with recurrent spontaneous abortions in humans and fetal loss in mice [37] [38] [39]. These cytokines are also found in normal decidual and placental tissues, and accumulating evidence suggests physiological roles for these factors in regulating trophoblast invasion, spiral artery modification, and placental morphogenesis [14] [40] [41]. "
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    • "BALB/c female pregnant mice infected with 106 CFU of B. abortus virulent strain 2308 develop a moderate multifocal necrotic placentitis associated with severe neutrophilic infiltrate and intralesional bacteria in trophoblastic cells [54]. The bacterial load and lesions described in the placenta increase throughout the pregnancy, whereas the bacterial load recovered from the spleen was stable during the course of infection in the mouse [54, 65]. The lesions described in female pregnant mice were similar to those observed in cows, which suggests that this model may be useful to study Brucella-induced placental disease, although mice and cattle have different morphological types of placenta [54]. "
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