Listeria monocytogenes Inoculation Impedes the Development of Brain Pathology in Experimental Cerebral Malaria by Inhibition of Parasitemia

Cerebral malaria (CM) is a serious central nervous system dysfunction caused by Plasmodium falciparum infection. In this study, we investigated the effect of Listeria monocytogenes (Lm) inoculation on experimental cerebral malaria (ECM) using Plasmodium berghei ANKA (PbA)-infected C57BL/6 mice. Live Lm inoculation inhibited the parasitemia and alleviated ECM symptoms. The protective effect against ECM symptoms was connected with improved brain pathology manifested as a less-damaged blood–brain barrier, decreased parasite sequestration, and milder local inflammation. Meanwhile, Lm inoculation decreased expression of cell adhesion molecules (ICAM-1 and VCAM-1) and accumulation of pathogenic CD8⁺ T cells in the brain. In keeping with the suppression of parasitemia, there was an upregulation of IFN-γ, IL-12, MCP-1, and NO expression in the spleen by Lm inoculation upon PbA infection. Early treatment with exogenous IFN-γ exhibited a similar effect to Lm inoculation on PbA infection. Taken together, Lm inoculation impedes the development of brain pathology in ECM, and early systemic IFN-γ production may play a critical role in these protective effects.