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

@article{citeulike:2798860, abstract = {Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune 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 (PbA). 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 IFNgamma, IL10 and IL6 were significantly higher in the serum of B6 mice than CBA mice at ECM. Two therapeutic strategies were applied to B6 and CBA mice, that is: 1) depletion of regulatory T (Treg) cells prior to infection; and 2) 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.}, address = {Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia; School of Population Health, Public Health Building, University of Queensland, Herston Road, Herston, QLD 4006, Australia.}, author = {Randall, Louise M M. and Amante, Fiona H H. and McSweeney, Karli A A. and Zhou, Yonghong and Stanley, Amanda C C. and Haque, Ashraful and Jones, Malcolm K K. and Hill, Geoff R R. and Boyle, Glen M M. and Engwerda, Christian R R. }, citeulike-article-id = {2798860}, doi = {10.1128/IAI.01475-07}, issn = {1098-5522}, journal = {Infection and immunity}, keywords = {pb}, month = {May}, posted-at = {2008-05-15 10:27:16}, priority = {2}, title = {Common Strategies to prevent and modulate experimental cerebral malaria in different susceptible mouse strains.}, url = {http://dx.doi.org/10.1128/IAI.01475-07}, year = {2008} }

TY - JOUR ID - citeulike:2798860 L3 - citeulike-article-id:2798860 TI - Common Strategies to prevent and modulate experimental cerebral malaria in different susceptible mouse strains. JF - Infection and immunity AD - Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia; School of Population Health, Public Health Building, University of Queensland, Herston Road, Herston, QLD 4006, Australia. SN - 1098-5522 N2 - Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, predominantly experienced by children and non-immune 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 (PbA). 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 IFNgamma, IL10 and IL6 were significantly higher in the serum of B6 mice than CBA mice at ECM. Two therapeutic strategies were applied to B6 and CBA mice, that is: 1) depletion of regulatory T (Treg) cells prior to infection; and 2) 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. KW - pb AU - Randall, Louise M AU - Amante, Fiona H AU - McSweeney, Karli A AU - Zhou, Yonghong AU - Stanley, Amanda C AU - Haque, Ashraful AU - Jones, Malcolm K AU - Hill, Geoff R AU - Boyle, Glen M AU - Engwerda, Christian R PY - 2008/05/12/ UR - http://dx.doi.org/10.1128/IAI.01475-07 ER -