Tohoku J. Exp. Med., 2014 December, 234(4)

Early Treatment with Chloroquine Inhibits the Immune Response against Plasmodium yoelii Infection in Mice

XIAOSONG QIN,^1,2 GUANG CHEN,³ YONGHUI FENG,⁴ XIAOTONG ZHU,¹ YUNTING DU,¹ WEI PANG,¹ ZANMEI QI¹ and YAMING CAO¹

¹Department of Immunology, College of Basic Medical Sciences, China Medical University, Heping District, Shenyang, Liaoning, P.R. China
²Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China
³Department of Parasitology, College of Basic Medical Sciences, Jamusi University, Jamusi, Heilongjiang, P.R. China
⁴Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China

Chloroquine (CQ), a well-known anti-malarial drug, has long been used for the treatment of autoimmune diseases because of its profound immunomodulatory effects. However, whether this drug modifies anti-malaria immune response is still not clear. Here we studied the immunomodulatory role of CQ in a mouse model of malaria. DBA/2 mice were infected with Plasmodium yoelii (Py) parasite (intraperitoneal injection of parasitized erythrocytes) and divided into three groups. Two groups received single dose of CQ (gavage administration) at 6 hours after Py infection (post-6h) and 3 days after Py infection (post-3d), respectively. The third group received saline as control. The course of disease was monitored and the changes of immune response were investigated. It is shown that mice from the post-6h group took longer time to clear the parasites compared with those of the post-3d group. The activation of T helper cells, macrophages, and B cells was significantly suppressed in mice with post-6h CQ treatment as compared with control mice on day 3 and day 5 after infection. In contrast, no such changes were found in mice from the post-3d group. Dendritic cells (DCs) from the post-6h CQ treated mice were less mature as compared with those from control mice as well as those from the post-3d group. Taken together, our data suggest that treatment with CQ early in infection inhibits protective immune response against Py infection possibly via mechanisms involving the modulation of DC's function. Our finding provided important information for reasonable use of CQ in malaria chemotherapy.

keywords —— chloroquine; early infection; immune response; immune suppression; Plasmodium yoelii 17XL

© 2014 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2014, 234, 271-280

Correspondence: Yaming Cao, Department of Immunology, College of Basic Medical Sciences, China Medical University, No. 92 Beier Road, Heping District, Shenyang, Liaoning 110001, P.R. China.

e-mail: ymcao@mail.cmu.edu.cn