Effect of Hydroxychloroquine in a Mouse Model of Abortion Caused by Brucella abortus Infection.

Hydroxychloroquine (HCQ) has showed beneficial effects on pregnancy outcomes in systemic erythaematosus lupus (SLE) by its anti-inflammatory and immunomodulatory properties. However, the role of HCQ in preventing abortion caused by infectious diseases remains unknown. In this study, we choose B. abortus-induced abortion of pregnant mice as a model to investigate the effect of HCQ in preventing abortion. HCQ decreases the pH value of endosomal Brucella-containing vacuole (eBCV), B. abortus type IV secretion system (T4SS) expression in trophoblasts and Brucella intracellular growth and cell death. Moreover, administration of HCQ decreases inflammation triggered by dead trophoblasts in a T4SS-independent manner. Mechanistically, this suppressed inflammatory response is due to inhibition of both NF-kB and mitogen-activated protein kinases (MAPKs) activation by HCQ. In the murine model of abortion, HCQ treatment enhanced pup viability through suppressing B. abortus growth within placenta and preventing placentitis. Our results suggest administration of HCQ could be an effective protection against abortion induced by Brucella infection, which imply that HCQ may be beneficial in treating abortion caused by infectious diseases.