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, Channe Gowda, Ruili Huang, Timothy G. Myers, Carole A. Long, Rong Fu Wang, Xin Zhuan Su

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Malaria infection induces complex and diverse immune responses. To elucidate the mechanisms underlying host–parasite interaction, we performed a genetic screen during early (24 h) Plasmodium yoelii infection in mice and identified a large number of interacting host and parasite genes/loci after transspecies expression quantitative trait locus (Ts-eQTL) analysis. We next investigated a host E3 ubiquitin ligase gene (March1) that was clustered with interferon (IFN)-stimulated genes (ISGs) based on the similarity of the genome-wide pattern of logarithm of the odds (LOD) scores (GPLS). March1 inhibits MAVS/STING/TRIF-induced type I IFN (IFN-I) signaling in vitro and in vivo. However, in malaria-infected hosts, deficiency of March1 reduces IFN-I production by activating inhibitors such as SOCS1, USP18, and TRIM24 and by altering immune cell populations. March1 deficiency increases CD86+DC (dendritic cell) populations and levels of IFN-γ and interleukin 10 (IL-10) at day 4 post infection, leading to improved host survival. T cell depletion reduces IFN-γ level and reverse the protective effects of March1 deficiency, which can also be achieved by antibody neutralization of IFN-γ. This study reveals functions of MARCH1 (membrane-associated ring-CH–type finger 1) in innate immune responses and provides potential avenues for activating antimalaria immunity and enhancing vaccine efficacy.

Original languageEnglish (US)
Pages (from-to)16567-16578
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - Jul 14 2020


  • Host–parasite interaction
  • Innate response
  • Interferons
  • Plasmodium

ASJC Scopus subject areas

  • General


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