Lymphotoxin-α orchestrate hypoxic and immune factors to induces Experimental Cerebral Malaria-Inhibition mitigates pathogenesis, neurodegeneration and increases survival

Abstract

Abstract Knockdown studies have shown lymphotoxin-α (Lt-α) as a critical molecule for Experimental cerebral malaria (ECM) pathogenesis. We investigated the role of lymphotoxin-α in regulating active caspase-3 and calpain1. T cell infiltration into the brains, and subsequent neuronal cell death are the essential features of Plasmodium berghei ANKA(PbA) induced ECM in C57BL/6 mice. Our results showed increased Lt-α levels during ECM. Treatment of naïve mice with serum from ECM mice and exogenous Lt-α was lethal. We inhibited Lt-α in vivo during PbA infection by injecting the mice with anti-Lt-α antibody. Inhibition of Lt-α mitigated neuronal cell death and increased mice's survival until 30 days post-infection (p.i) compared to only 15 days survival of PbA control mice.