Malaria remains a global health burden, with >212 million cases and 429,000 deaths annually. Current control strategies rely largely on antimalarial drugs such as chloroquine and artemisinin based combination therapies (ACTs), though ongoing emergence of resistance highlights the need for development of effective antimalaria vaccines.

Anti-Plasmodium antibody responses are short lived and dominated by extrafollicular, IgM-secreting B cell reactions, and as a result, sterilizing immunity against Plasmodium rarely develops in humans, even following repeated parasite exposure. We are testing the hypothesis that Plasmodium-specific memory CD4 T cell responses are functionally deficient, thus explaining weak and short-lived cellular and antibody immunity against this infection. Using Plasmodium specific CD4 T cells, we are assessing the temporal contributions of associated cytokines during acute and chronic Plasmodium infection, as well as their impact on CD4 T cell memory formation.

Vijay, R. V., Guthmiller, J. J., Sturtz, A. J., Surette, F. A., Rogers, K. J...Butler, N. S. 2020. Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria. Nature Immunol. doi:10.1038/s41590-020-0678-5

Surette, F. A., Guthmiller, J. J., Lei, L., Sturtz, A. J., Vijay, R., et al.  Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity. PLoS Pathogens. 2021; 17(2):e1009288. DOI: 10.1371/journal.ppat.1009288

Lefebvre, M. N., Surette, F. A., Anthony, S. M., Vijay, R., Jensen, I. J., Pewe, L. L., Hancox, L. S., Van Braeckel-Budimir, N., Van de Wall, S., Urban, S., Mix, M. R., Kurup, S. P., Badovinac, V. P., Butler, N. S., Harty, J. T. 2021. Expeditious recruitment of circulating memory CD8 T cells to the liver facilitates control of malaria. Cell Rep. 37(5):109956. Doi: 10. 1016/j.celrep.2021.109956.

Surette, F. A., Butler, N. S. 2022. Temporally evolving and context-dependent functions of cytokines that regulate murine anti-Plasmodium humoral immunity. Pathogens. 11(5), 523. Doi: 10.3390/pathogens11050523