Emerging concepts in T follicular helper cell responses to malaria.

Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of TFH cells in malaria could illuminate strategies to improve vaccines through modulating TFH cell responses. This review summarizes emerging concepts in TFH cell responses to malaria.