T follicular helper cell development during malaria

Malaria is a life-threatening disease affecting more than 200 million people worldwide. CD4 T helper 1 (Th1) and T follicular helper (Tfh) cells are critical for stimulating phagocyte activation and humoral immunity, yet sterilizing, protective immune memory responses rarely develop. Malaria induces unique physiologic changes in the infected host that may give rise to nonconventional Tfh subsets and inefficient memory responses. While our understanding of the differentiation of conventional Tfh cells induced by Plasmodium infection is growing, how and whether malaria-associated environmental cues induce Tfh populations exhibiting mixed phenotype and function are not well defined. Moreover, little is known about the development and function of Tfh memory cells during malaria. In this review, we discuss the phenotype and known functions of Tfh subsets and memory development induced during malaria and highlight key priority knowledge gaps that remain to be addressed.