Gene Expression Profile of THP-1 Cells Infected by R. prowazekii Suggests Host Response Signature Genes



Hong Ge1, *, Shuping Zhao2, Xing Lü2, Eric Yao-Yu Chuang3, 4, Wei-Mei Ching1, 5
1 Viral and Rickettsial Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910, USA
2 Microarray Laboratory, Radiation Oncology Sciences Program, National Cancer Institute, National Institutes of Health, Gaithersburg, Maryland 20877, US
3 Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
4 Graduate Institute of Bioelectronics and Bioinformatics, Department of Electrical Engineering, Center for Genomic Medicine, National Taiwan University, Taipei, Taiwan
5 Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA


© 2008 Ge et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Bldg. 503, Rm 3N66, VRDD, IDD, NMRC, Silver Spring, MD20910, USA.E-mail: geh@nmrc.navy.mil.com


Abstract

Rickettsia prowazekii, a selective agent of category B, is the causative microorganism of epidemic typhus. The genome-wide profile of host response to R. prowazekii infection was studied in THP-1 cells by a human cDNA microarray. Approximately 131 (1.71%) and 11 (0.14%) genes out of 7,680 genes assessed were up-regulated or down-regulated upon infection with virulent R. prowazekii strain Breinl. These genes induced by R. prowazekii were diverse in function. Six genes [ENG (endoglin or CD105, cell surface glycoprotein), GADD45A, TNFAIP3, IGFBP3, POU3F4 (transcription), ELK3] were identified as commonly induced genes as their over expressions were observed throughout the entire time course studied. There were twenty-two genes [such as GADD45A, POU3F4, ENG, PPP1R14B (an enzyme), ELK3, CXCL1, IL1B, NFKB1A, etc.] that exhibited the high level of induction at more than one time point. Collectively, these discoveries may provide novel insights into mechanisms of rickettsial pathogenesis and might reveal potential therapeutic targets against rickettsial infection.