Abstract
The pathogenesis of the Brucella-induced inflammatory response in the bovine placenta is not completely understood. In this study we evaluated the role of the B. abortus Type IV secretion system and the anti-inflammatory factor BtpB in early interactions with bovine placental tissues. Transcription profiles of chorioallantoic membrane (CAM) explants inoculated with wild type (strain 2308), ΔvirB2 or ΔbtpB Brucella abortus were compared by microarray analysis at 4 hours post infection. Transcripts with significant variation (>2 fold change; P<0.05) were functionally classified, and transcripts related to defense and inflammation were assessed by quantitative real time RT-PCR. Infection with wild type B. abortus resulted in slightly more genes with decreased than increased transcription levels. Conversely, infection of trophoblastic cells with the ΔvirB2 or the ΔbtpB mutant strains, that lack a functional T4SS or that has impaired inhibition of TLR signaling, respectively, induced more upregulated than downregulated genes. Wild type Brucella abortus impaired transcription of host genes related to immune response when compared to ΔvirB and ΔbtpB mutants. Our findings suggest that proinflammatory genes are negatively modulated in bovine trophoblastic cells at early stages of infection. The virB operon and btpB are directly or indirectly related to modulation of these host genes. These results shed light on the early interactions between B. abortus and placental tissue that ultimately culminate in inflammatory pathology and abortion.
Highlights
Brucellosis is an important zoonotic disease with worldwide distribution, caused by bacteria of the genus Brucella
In order to evaluate whether the Brucella strains used in this study had comparable levels of internalization in trophoblastic cells of bovine chorioallantoic membrane (CAM) explants, colony forming units (CFU) numbers at 4 h post inoculation followed by 1 h of incubation with gentamicin
Considering that B. abortus modulates the innate immune response of bovine trophoblastic cells [13], and that TIR domaincontaining Brucella proteins, such as BtpB have been shown to impair the host innate immune response [19], whereas the virBencoded T4SS is required for Brucella survival within host cells [26], a comparison of the transcription profile of bovine trophoblastic cells infected with wild type B. abortus, or the isogenic DvirB2 or DbtpB strains was performed in this study
Summary
Brucellosis is an important zoonotic disease with worldwide distribution, caused by bacteria of the genus Brucella. Most cases of bovine brucellosis are due to Brucella abortus infection, which is transmitted by contact with contaminated aborted fetuses, fetal membranes, and uterine secretions after abortion or during the postpartum period [4,5]. B. abortus triggers an intense acute inflammatory response in the placenta, which is associated with abortion [7]. While this inflammatory pathology is well-described, very little is known about the initial interactions between B. abortus and placental cells that result in placentitis and abortion, two processes that are key components of disease transmission. Because of the difficulty of studying these early interactions in pregnant animals, ex vivo infection of cultured chorioallantoic membrane (CAM) explants, which results in localization of B. abortus to trophoblasts, has been used to study the initial phases of placental infection [12,13]
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