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 (T_FH) 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 T_H1 cytokines are associated with the activation of (i) T-like memory T_FH cells with impaired B cell helper function, and (ii) pre-T_FH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional T_FH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of T_FH cells in malaria could illuminate strategies to improve vaccines through modulating T_FH cell responses. This review summarizes emerging concepts in T_FH cell responses to malaria.