Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response
Jian Wu,
Baowei Cai,
Wenxiang Sun,
Ruili Huang,
Xueqiao Liu,
Meng Lin,
Sittiporn Pattaradilokrat,
Scott Martin,
Yanwei Qi,
Sethu C. Nair,
Silvia Bolland,
Jeffrey I. Cohen,
Christopher P. Austin,
Carole A. Long,
Timothy G. Myers,
Rong-Fu Wang,
Xin-zhuan Su
Affiliations
Jian Wu
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Baowei Cai
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PRC
Wenxiang Sun
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Ruili Huang
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA
Xueqiao Liu
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Meng Lin
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA
Sittiporn Pattaradilokrat
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Scott Martin
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA
Yanwei Qi
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Sethu C. Nair
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Silvia Bolland
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Jeffrey I. Cohen
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Christopher P. Austin
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA
Carole A. Long
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Timothy G. Myers
Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Rong-Fu Wang
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA
Xin-zhuan Su
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA
Invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. In this study, we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly linked 1,054 host genes to parasite genetic loci (LOD score ≥ 3.0). Using LOD score patterns, which produced results that differed from direct expression-level clustering, we grouped host genes that function in related pathways, allowing functional prediction of unknown genes. As a proof of principle, 14 of 15 randomly selected genes predicted to function in type I interferon (IFN-I) responses were experimentally validated using overexpression, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.
