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Predominance of Interferon-Related Responses in the Brain during Murine Malaria, as Identified by Microarray Analysis ^,

Jenny Miu, Nicholas H. Hunt,^* and Helen J. Ball

Molecular Immunopathology Unit, Bosch Institute, University of Sydney, Sydney, Australia

Received 11 December 2007/ Returned for modification 2 February 2008/ Accepted 18 February 2008

Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. We examined global gene expression patterns during fatal murine CM (FMCM) and noncerebral malaria (NCM) by microarray analysis. There was differential expression of a number of genes, including some not yet characterized in the pathogenesis of FMCM. Some gene induction was observed during Plasmodium berghei infection regardless of the development of CM, and there was a predominance of genes linked to interferon responses, even in NCM. However, upon real-time PCR validation and quantitation, these genes were much more highly expressed in FMCM than in NCM. The observed changes included genes belonging to pathways such as interferon signaling, major histocompatibility complex processing and presentation, apoptosis, and immunomodulatory and antimicrobial processes. We further characterized differentially expressed genes by examining the cellular source of their expression as well as their temporal expression patterns during the course of malaria infection. These data identify a number of novel genes that represent interesting candidates for further investigation in FMCM.

Published ahead of print on 25 February 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. F. Urban, Jr.

Present address: Department of Medicine, McGill University, Montreal, Quebec, Canada.