Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 224, Issue 3, Pages 532-543Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiaa722
Keywords
Brucella abortus; progesterone; inflammation; placentitis
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Funding
- Natural Science Foundation of China [31870121]
- Fundamental Research Funds for the Central Universities
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Progesterone treatment reduces placentitis and enhances pup viability by inhibiting the secretion of inflammatory cytokines in serum, macrophages, and trophoblasts. The decreased inflammatory response is due to the inhibition of NF-kB activation by progesterone, which also suppresses Brucella growth within trophoblasts.
Progesterone has been recognized as essential for the establishment and maintenance of pregnancy, and is typically known as an immuno-suppressive agent. However, its effects on mediating Brucella infection-induced inflammation have not been evaluated. Here we demonstrated that Brucella abortus infection inhibits progesterone levels in the pregnant mouse by suppressing the production of progesterone by placenta. Progesterone treatment significantly reduced the secretion of inflammatory cytokines in serum, macrophages, and trophoblasts of B. abortus-infected mice, leading to decreased placentitis and enhancing the pup viability. Mechanistically, this decreased inflammatory response results from inhibition of NF-kB activation by progesterone. Moreover, progesterone treatment suppresses B. abortus growth within trophoblasts associated with an inability of bacteria to escape the late endosome compartment in vitro. Collectively, our data illustrate that progesterone treatment might be useful therapeutically in protection against placentitis or abortion caused by B. abortus infection.
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