Effect of Hydroxychloroquine in a Mouse Model of Abortion Caused by <i>Brucella abortus</i> 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 <i>B. abortus</i>-induced abortion of pregnant mice as a model to investigate the effect of HCQ in preventing abortion. HCQ decreases the pH value of endosomal <i>Brucella</i>-containing vacuole (eBCV), <i>B. abortus</i> type IV secretion system (T4SS) expression in trophoblasts and <i>Brucella</i> 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 <i>B. abortus</i> growth within placenta and preventing placentitis. Our results suggest administration of HCQ could be an effective protection against abortion induced by <i>Brucella</i> infection, which imply that HCQ may be beneficial in treating abortion caused by infectious diseases.