Early Treatment with Chloroquine Inhibits the Immune Response against<i> Plasmodium yoelii</i> Infection in Mice

Abstract

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 antimalaria 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.

An unexpected, revolutionary property of Artemisia infusions: immunoglobulins in the skin lead to a longlasting prophylaxis

“…The authors conclude that chloroquine only is efficient in the well-established erythrocytic stage by inhibiting hemozoin formation, but, if used in prophylaxis, may have dramatic impacts on the immune system and malaria prevalence. 202 This is not surprising as chloroquine reduces CD4+ activation. 203…”

Antibodies, prophylaxis, transmission

“…The authors conclude that chloroquine only is efficient in the well established erythrocytic stage by inhibiting hemozoin formation, but, if used in prophylaxis, may have dramatic impacts on the immune system and malaria prevalence. 46 This is not surprising as chloroquine reduces CD4 + activation. 47 Is it criminal negligence not to have studied in the European Institutes of Tropical Medicine and elsewhere the impact of this inhibition of the immune system might have on prophylaxis and transmission and to have alerted the African communities against these risks.…”

Autophagy in Tumor Immunity and Viral-Based Immunotherapeutic Approaches in Cancer

“…Briefly, hydroxychloroquine and chloroquine dampen TLR signaling and interfere with antigen processing, MHCII expression, and presentation with a consequent reduction in T-cell activation, cytokine production, and effector functions [174,175]. In mouse models of malaria, chloroquine significantly suppresses macrophage, B-cell, and helper T-cell activation while dampening DC maturation [176]. Inhibition of many aspects of innate immunity leads to reduced type I IFN and other pro-inflammatory cytokine responses, including TNF-α, IL-6, and IL-1β, which result in dampened adaptive immune responses [177].…”