The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation
| Autor: | Chen Feng Qi, Yu Chih Peng, Yang Cheng, Xiangyu Yao, Sonja M. Best, Xiao He, Timothy G. Myers, Lu Xia, Cui Zhang, Ruili Huang, Wenxiang Sun, Brajesh K. Singh, Rong Fu Wang, Carole A. Long, Keyla C. Tumas, Jian Wu, Silvia Bolland, Channe Gowda, Xin-zhuan Su, Xiao Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
T-Lymphocytes Ubiquitin-Protein Ligases T cell Host-Parasite Interactions Interferon-gamma Mice Immune system Immunity Interferon medicine Animals Humans Mice Knockout Multidisciplinary Innate immune system biology Plasmodium yoelii Dendritic cell Biological Sciences biology.organism_classification Immunity Innate Interleukin-10 Malaria Cell biology Ubiquitin ligase Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Interferon Type I biology.protein Female medicine.drug |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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