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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Innate immune responses to human malaria: Heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes
Journal of Immunology, Volume 177, No. 8, Year 2006
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Description
Taking advantage of a sporozoite challenge model established to evaluate the efficacy of new malaria vaccine candidates, we have explored the kinetics of systemic cytokine responses during the prepatent period of Plasmodium falciparum infection in 18 unvaccinated, previously malaria-naive subjects, using a highly sensitive, bead-based multiplex assay, and relate these data to peripheral parasite densities as measured by quantitative real-time PCR. These data are complemented with the analysis of cytokine production measured in vitro from whole blood or PBMC, stimulated with P. falciparum-infected RBC. We found considerable qualitative and quantitative interindividual variability in the innate responses, with subjects falling into three groups according to the strength of their inflammatory response. One group secreted moderate levels of IFN-γ and IL-10, but no detectable IL-12p70. A second group produced detectable levels of circulating IL-12p70 and developed very high levels of IFN-γ and IL-10. The third group failed to up-regulate any significant proinflammatory responses, bat showed the highest levels of TGF-β. Proinflammatory responses were associated with more rapid control of parasite growth but only at the cost of developing clinical symptoms, suggesting that the initial innate response may have far-reaching consequences on disease outcome. Furthermore, the in vitro observations on cytokine kinetics presented here, suggest that intact schizont-stage infected RBC can trigger innate responses before rupture of the infected RBC. Copyright © 2006 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Walther, Michael
Unknown Affiliation
Woodruff, John
Unknown Affiliation
Edele, Fanny
Unknown Affiliation
Jeffries, David J.
Unknown Affiliation
Tongren, Jon Eric
Unknown Affiliation
King, Elizabeth C.
Unknown Affiliation
Andrews, Laura
Unknown Affiliation
Bejon, Philip A.
Unknown Affiliation
Gilbert, Sarah C.
Unknown Affiliation
de Souza, Joseph Brian
Unknown Affiliation
Sinden, Robert E.
Unknown Affiliation
Hill, Adrian V. S.
Unknown Affiliation
Riley, Eleanor M.
Unknown Affiliation
Statistics
Citations: 95
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.4049/jimmunol.177.8.5736
ISSN:
00221767
Research Areas
Infectious Diseases
Study Approach
Qualitative
Quantitative