IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Other Versions of this Article:
IAI.01475-07v1
76/7/3312    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Randall, L. M.
Right arrow Articles by Engwerda, C. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Randall, L. M.
Right arrow Articles by Engwerda, C. R.

 Previous Article  |  Next Article 

Infection and Immunity, July 2008, p. 3312-3320, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01475-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Common Strategies To Prevent and Modulate Experimental Cerebral Malaria in Mouse Strains with Different Susceptibilities{triangledown} ,{dagger}

Louise M. Randall,1,2 Fiona H. Amante,1 Karli A. McSweeney,1 Yonghong Zhou,1 Amanda C. Stanley,1 Ashraful Haque,1 Malcolm K. Jones,1 Geoff R. Hill,1 Glen M. Boyle,1 and Christian R. Engwerda1*

Queensland Institute of Medical Research, 300 Herston Road, Herston, Queensland 4006, Australia,1 School of Population Health, Public Health Building, University of Queensland, Herston Road, Herston, Queensland 4006, Australia2

Received 4 November 2007/ Returned for modification 13 December 2007/ Accepted 3 May 2008

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.

* Corresponding author. Mailing address: Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia. Phone: 61 7 3362 0428. Fax: 61 7 3362 0104. E-mail: Christian.Engwerda{at}qimr.edu.au

{triangledown} Published ahead of print on 12 May 2008.

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

Editor: J. F. Urban, Jr.

Infection and Immunity, July 2008, p. 3312-3320, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.01475-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2008 by the American Society for Microbiology. All rights reserved.