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Modulation of the Bovine Trophoblastic Innate Immune Response by Brucella abortus

Departamento de Clínica e Cirurgia Veterinária and Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil,¹ Department of Medical Microbiology and Immunology, University of California at Davis, Davis, California,² Department of Animal Sciences, University of Illinois, Urbana, Illinois,³ Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas,⁴ Instituto Ludwig de Pesquisa sobre o Câncer, São Paulo, SP, Brazil⁵

Received 23 November 2007/ Returned for modification 15 January 2008/ Accepted 30 January 2008

Brucellosis is still a widespread zoonotic disease. Very little is known about the interaction between Brucella abortus and trophoblastic cells, which is essential for better understanding the pathogenesis of the Brucella-induced placentitis and abortion, a key event for transmission of the disease. The goal of this study was to evaluate the profile of gene expression by bovine trophoblastic cells during infection with B. abortus. Explants of chorioallantoic membranes were inoculated with B. abortus strain 2308. Microarray analysis was performed at 4 h after infection, and expression of cytokines and chemokines by trophoblastic cells was assessed by real-time reverse transcription-PCR at 6 and 12 h after inoculation. In addition, cytokine and chemokine expression in placentomes from experimentally infected cows was evaluated. Expression of proinflammatory genes by trophoblastic cells was suppressed at 4 h after inoculation, whereas a significant upregulation of CXC chemokines, namely, CXCL6 (GCP-2) and CXCL8 (interleukin 8), was observed at 12 but not at 6 h after inoculation. Placentomes of experimentally infected cows had a similar profile of chemokine expression, with upregulation of CXCL6 and CXCL8. Our data indicate that B. abortus modulates the innate immune response by trophoblastic cells, suppressing the expression of proinflammatory mediators during the early stages of infection that is followed by a delayed and mild expression of proinflammatory chemokines, which is similar to the profile of chemokine expression in the placentomes of experimentally infected cows. This trophoblastic response is likely to contribute to the pathogenesis of B. abortus-induced placentitis.

Published ahead of print on 3 March 2008.

Editor: J. B. Bliska