Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response

• Main Authors: 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
• Format: Article
• Language: English
• Published: Elsevier 2015-07-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124715006841

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.