Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes.

Walther, M; Woodruff, J; Edele, F; Jeffries, D; Tongren, J; King, E; Andrews, L; Bejon, P; Gilbert, S; De Souza, J; Sinden, R; Hill, A; Riley, E

Journal article

Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes.

Abstract:: 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-gamma 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-gamma and IL-10. The third group failed to up-regulate any significant proinflammatory responses, but showed the highest levels of TGF-beta. 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.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Walther, M., Woodruff, J., Edele, F., Jeffries, D., Tongren, J., King, E., Andrews, L., Bejon, P., Gilbert, S., De Souza, J., Sinden, R., Hill, A., & Riley, E. (2006). Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. Journal of Immunology, 177(8), 5736–5745.

MLA Style

Walther, M, et al. “Innate Immune Responses to Human Malaria: Heterogeneous Cytokine Responses to Blood-Stage Plasmodium Falciparum Correlate with Parasitological and Clinical Outcomes.” Journal of Immunology, vol. 177, no. 8, 2006, pp. 5736–45.

Chicago Style

Walther, M, J Woodruff, F Edele, et al. 2006. “Innate Immune Responses to Human Malaria: Heterogeneous Cytokine Responses to Blood-Stage Plasmodium Falciparum Correlate with Parasitological and Clinical Outcomes.” Journal of Immunology 177 (8): 5736–45.
Print