γδ T cells in malaria: a double‐edged sword

Abstract

Malaria remains a devastating global health problem, resulting in many annual deaths due to the complications of severe malaria. However, in endemic regions, individuals can acquire 'clinical immunity' to malaria, characterized by a decrease in severe malaria episodes and an increase of asymptomatic Plasmodium falciparum infections. Recently, it has been reported that tolerance to 'clinical malaria' and reduced disease severity correlates with a decrease in the numbers of circulating Vc9Vd2 T cells, the major subset of cd T cells in the human peripheral blood. This is particularly interesting as this population typically undergoes dramatic expansions during acute Plasmodium infections and was previously shown to play antiparasitic functions. Thus, regulated cd T-cell responses may be critical to balance immune protection with severe pathology, particularly as both seem to rely on the same pro-inflammatory cytokines, most notably TNF and IFN-c. This has been clearly demonstrated in mouse models of experimental cerebral malaria (ECM) based on Plasmodium berghei ANKA infection. Furthermore, our recent studies suggest that the natural course of Plasmodium infection, mimicked in mice through mosquito bite or sporozoite inoculation, includes a major pathogenic component in ECM that depends on cd T cells and IFN-c production in the asymptomatic liver stage, where parasite virulence is seemingly set and determines pathology in the subsequent blood stage. Here, we discuss these and other recent advances in our understanding of the complex-protective versus pathogenic-functions of cd T cells in malaria.

Innate and adaptive γδ T cells: How, when, and why

“…Taken together, we propose that the first wave of T cells made by the human fetus, the Vγ9Vδ2 T cell subset, provides protection of the human fetus and newborn against infections in utero and early after birth. This does not exclude a possible immunopathological role of these cells like in conditions such as in sepsis of (premature) newborns and infants (123)(124)(125), which requires further investigation.…”

Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection

“…This was particularly apparent after the fifth immunization, although this difference was not statistically significant. While this may appear at odds with the described protective role of Vd2 gdT cells, other work suggests a complex relationship between Vd2 gdT and malaria immunity: it has been reported that a decrease in Vd2 gdT cells levels is associated with tolerance [55] and reduced severity of malaria infection [56]. We previously observed a detrimental role of type I interferon in the development of malaria protection after prime immunization and a correlation between it and non-classical monocytes.…”

Properties and Roles of γδT Cells in Plasmodium yoelii nigeriensis NSM Infected C57BL/6 Mice

“…γδT cells play an important role in resisting malaria infection in humans and mice ( Pamplona and Silva-Santos, 2020 ). In this study, the properties of γδT cells were investigated in P. yoelii NSM infected C57BL/6 mice.…”

“…Plasmodium infection could induce “memory-like imprints” in γδ T cells to promote γδ T cell mediated antigen presentation during subsequent infections ( Kumarasingha et al., 2020 ). Regulated γδT cell responses may be critical to balance immune protection with severe pathology rely on proinflammatory cytokines, such as IFN-γ ( Pamplona and Silva-Santos, 2020 ).…”