Abstract
Plasmodium chabaudi chabaudi AS blood stage infection results in various degrees of clinical symptoms to malaria depending on the mouse strain. This study aimed to investigate the development of memory responses in susceptible A/J and resistant C57BL/6 mice which differ in the degree of susceptibility to clinical malaria following P. chabaudi AS infection. A rapid increase of activated cells (CD25+, CD44high, and CD62Llow) and production of both interferon-γ and interleukin-4 was found in spleens of both malaria-infected mouse strains. After the parasitemia had been cleared, these activated cells were converted to their resting phenotypes. Although exhibiting susceptible phenotype and having lower magnitude of cellular changes during primary infection, susceptible A/J mice that had been exposed to malaria parasites and drug-cured were able to generate protective immunity capable of control parasite growth following reinfection to the same level as C57BL/6 mice. This may be due to the capability of susceptible mice to produce parasite-specific antibodies, in particular of the IgG2a and IgG3 isotypes. The results from this study may provide more insights useful for the development of vaccines against malaria.
References
Achtman AH, Stephens R, Cadman ET, Harrison V, Langhorne J (2007) Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi. Parasite Immunol 29:435–444
Cambos M, Belanger B, Jacques A, Roulet A, Scorza T (2008) Natural regulatory (CD4 + CD25 + FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion. Int J Parasitol 38:229–238
Freitas do Rosario AP, Muxel SM, Rodriguez-Malaga SM, Sardinha LR, Zago CA, Castillo-Mendez SI, Alvarez JM, D'Imperio Lima MR (2008) Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol 181:8344–8355
Langhorne J, Cross C, Seixas E, Li C, von der Weid T (1998) A role for B cells in the development of T cell helper function in a malaria infection in mice. Proc Natl Acad Sci USA 95:1730–1734
Meding SJ, Langhorne J (1991) CD4+ T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi. Eur J Immunol 21:1433–1438
Mohan K, Moulin P, Stevenson MM (1997) Natural killer cell cytokine production, not cytotoxicity, contributes to resistance against blood-stage Plasmodium chabaudi AS infection. J Immunol 159:4990–4998
Pouniotis DS, Proudfoot O, Bogdanoska V, Apostolopoulos V, Fifis T, Plebanski M (2004) Dendritic cells induce immunity and long-lasting protection against blood-stage malaria despite an in vitro parasite-induced maturation defect. Infect Immun 72:5331–5339
Seixas E, Cross C, Quin S, Langhorne J (2001) Direct activation of dendritic cells by the malaria parasite, Plasmodium chabaudi chabaudi. Eur J Immunol 31:2970–2978
Stephens R, Ndungu FM, Langhorne J (2009) Germinal centre and marginal zone B cells expand quickly in a second Plasmodium chabaudi malaria infection producing mature plasma cells. Parasite Immunol 31:20–31
Stevenson MM, Tam MF (1993) Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol 92:77–83
Stevenson MM, Lyanga JJ, Skamene E (1982) Murine malaria: genetic control of resistance to Plasmodium chabaudi. Infect Immun 38:80–88
Su Z, Stevenson MM (2002) IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. J Immunol 168:1348–1355
Taylor-Robinson AW, Phillips RS (1994) B cells are required for the switch from Th1- to Th2-regulated immune responses to Plasmodium chabaudi chabaudi infection. Infect Immun 62:2490–2498
Walker LS (2004) CD4+ CD25+ Treg: divide and rule? Immunology 111:129–137
Walther M, Tongren JE, Andrews L, Korbel D, King E, Fletcher H, Andersen RF, Bejon P, Thompson F, Dunachie SJ, Edele F, de Souza JB, Sinden RE, Gilbert SC, Riley EM, Hill AV (2005) Upregulation of TGF-beta, FOXP3, and CD4 + CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23:287–296
WHO (2009) Malaria Fact sheet. vol 2009
Wipasa J, Xu H, Stowers A, Good MF (2001) Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection. J Immunol 167:3903–3909
Wipasa J, Hirunpetcharat C, Mahakunkijcharoen Y, Xu H, Elliott S, Good MF (2002) Identification of T cell epitopes on the 33-kDa fragment of Plasmodium yoelii merozoite surface protein 1 and their antibody-independent protective role in immunity to blood stage malaria. J Immunol 169:944–951
Acknowledgment
We thank Dr. Chakrit Hirunpetcharat and Dr. Julius Hafalla for helpful discussion and accurate revision of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
This investigation received financial support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases and Thailand Tropical Diseases Research Programme (T-2).
Rights and permissions
About this article
Cite this article
Wipasa, J., Hemsokana, P., Ruankham, T. et al. Investigation of memory responses following Plasmodium chabaudi AS infection in mice distinct in susceptibility to clinical malaria. Parasitol Res 106, 283–287 (2009). https://doi.org/10.1007/s00436-009-1597-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-009-1597-4