The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation
Jian Wu, Lu Xia, Xiangyu Yao, Xiao Yu, Keyla C. Tumas, Wenxiang Sun, Yang Cheng, Xiao He, Yu‐Chih Peng, Brajesh K. Singh, Cui Zhang, Chen‐Feng Qi, Silvia Bolland, Sonja M. Best, D. Channe Gowda, Ruili Huang, Timothy G. Myers, Carole A. Long, Rong‐Fu Wang, Xin‐zhuan Su
Abstract
Significance Malaria kills ∼0.4 million people a year. Malaria parasite infection triggers complex immune responses that may control the infection or result in severe disease. The molecular mechanisms underlying host–parasite interaction and immune regulation are not completely understood. We perform a genome-wide genetic screen during early Plasmodium yoelii infection in mice and identify a large number of host and parasite genes/loci for future studies of the complex host–parasite interactions. We next investigate the functions of one of these host genes that encodes an E3 ubiquitin ligase (MARCH1). We show that MARCH1 regulates type I interferon signaling, T cell activation, and IFN-γ production during malaria infections. MARCH1 is a key molecule in immune responses and a potential target for immunotherapies.