Common strategies to prevent and modulate experimental cerebral malaria in different susceptible mouse strains

Randall, Louise M., Amante, Fiona H., McSweeney, Karli A., Zhou, Yonghong, Stanley, Amanda C., Haque, Ashraful, Jones, Malcolm K., Hill, Geoff R., Boyle, Glen M. and Engwerda, Christian R. (2008) Common strategies to prevent and modulate experimental cerebral malaria in different susceptible mouse strains. Infection and Immunity, 76 7: 3312-3320. doi:10.1128/IAI.01475-07

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Author Randall, Louise M.
Amante, Fiona H.
McSweeney, Karli A.
Zhou, Yonghong
Stanley, Amanda C.
Haque, Ashraful
Jones, Malcolm K.
Hill, Geoff R.
Boyle, Glen M.
Engwerda, Christian R.
Title Common strategies to prevent and modulate experimental cerebral malaria in different susceptible mouse strains
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 1098-5522
Publication date 2008-07-01
Year available 2008
Sub-type Article (original research)
DOI 10.1128/IAI.01475-07
Open Access Status File (Publisher version)
Volume 76
Issue 7
Start page 3312
End page 3320
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject 2405 Parasitology
2404 Microbiology
2403 Immunology
2725 Infectious Diseases
Abstract Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and nonimmune adults, which results in significant mortality and long-term sequelae. Previous studies have reported distinct susceptibility gene loci in CBA/CaH (CBA) and C57BL/6 (B6) mice with experimental CM (ECM) caused by infection with Plasmodium berghei ANKA. Here we present an analysis of genome-wide expression profiles in brain tissue taken from B6 and CBA mice with ECM and report significant heterogeneity between the two mouse strains. Upon comparison of the leukocyte composition of ECM brain tissue, microglia were expanded in B6 mice but not CBA mice. Furthermore, circulating levels of gamma interferon, interleukin-10, and interleukin-6 were significantly higher in the serum of B6 mice than in that of CBA mice with ECM. Two therapeutic strategies were applied to B6 and CBA mice, i.e., (i) depletion of regulatory T (Treg) cells prior to infection and (ii) depletion of CD8+ T cells after the establishment of ECM. Despite the described differences between susceptible mouse strains, depletion of Treg cells before infection attenuated ECM in both B6 and CBA mice. In addition, the depletion of CD8+ T cells when ECM symptoms are apparent leads to abrogation of ECM in B6 mice and a lack of progression of ECM in CBA mice. These results may have important implications for the development of effective treatments for human CM.
Keyword Immunology
Infectious Diseases
Infectious Diseases
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Public Health Publications
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 19 Mar 2009, 00:13:36 EST by Geraldine Fitzgerald on behalf of Faculty Of Health Sciences