@article{a5a0d80848014fd1b1d944996fe4d3ee,
title = "The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation",
abstract = "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.",
keywords = "Host–parasite interaction, Innate response, Interferons, Plasmodium",
author = "Jian Wu and Lu Xia and Xiangyu Yao and Xiao Yu and Tumas, {Keyla C.} and Wenxiang Sun and Yang Cheng and Xiao He and Peng, {Yu Chih} and Singh, {Brajesh K.} and Cui Zhang and Qi, {Chen Feng} and Silvia Bolland and Best, {Sonja M.} and Channe Gowda and Ruili Huang and Myers, {Timothy G.} and Long, {Carole A.} and Wang, {Rong Fu} and Su, {Xin Zhuan}",
note = "Funding Information: We thank Dr. Paul Roche of the NCI, NIH, and Dr. Satoshi Ishido of Japan for the March1-/- mice. This work was supported by the Division of Intramural Research, NIAID, NIH, and, in part, by grants from the NCI, NIH (R01CA101795 and U54CA210181), Department of Defense Congressionally Directed Medical Research Programs, Breast Cancer Research Program (BC151081), and startup funding from the Houston Methodist Research Institute and University of Southern California (to R.-F.W.). We thank Dr. Jacques Thibodeau for discussions/suggestions and Brigit Sullivan of the NIH library for editing. Funding Information: ACKNOWLEDGMENTS. We thank Dr. Paul Roche of the NCI, NIH, and Dr. Satoshi Ishido of Japan for the March1−/− mice. This work was supported by the Division of Intramural Research, NIAID, NIH, and, in part, by grants from the NCI, NIH (R01CA101795 and U54CA210181), Department of Defense Congressionally Directed Medical Research Programs, Breast Cancer Research Program (BC151081), and startup funding from the Houston Methodist Research Institute and University of Southern California (to R.-F.W.). We thank Dr. Jacques Thibodeau for discussions/suggestions and Brigit Sullivan of the NIH library for editing. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = jul,
day = "14",
doi = "10.1073/pnas.2004332117",
language = "English (US)",
volume = "117",
pages = "16567--16578",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "28",
}