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Biology subjects

Soon, M. S.

Publications and source records attributed to Soon, M. S..

2 recordsLinked to original sources

Comparison of CD4 T cell response in Plasmodium falciparum and vivax malaria

BackgroundPlasmodium falciparum and P. vivax are parasites responsible for most malaria cases globally. In areas where these species co-exist, individuals gain protection from P. vivax more rapidly, and important biological differences between species may impact the immune response. CD4 T cells are key drivers of immunity to malaria, both as effector and helper cells, with T-follicular helper (Tfh) having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited. MethodsWe assessed CD4 T cells in adults with either P. falciparum or P. vivax malaria. Activation and proliferation of CD4 T cells were measured ex vivo, and functional capacity determined by intracellular cytokine staining by flow cytometry. ResultsThe phenotype, activation and proliferation of CD4 T cells and effector CD4 T cell subsets were comparable between species. However, within the peripheral (p)Tfh cell compartment, there was evidence for a skew towards pTfh1 cells in P. falciparum, and pTfh2 cells in P. vivax. Additionally, in P. falciparum, increased IL-10 production was detected, including within IL-21 producing CD4 T cells. ConclusionWhile activation and function of CD4 T cells in malaria are largely comparable, some species-dependent responses are detected within the pTfh cell compartment that may impact antibody development.

immunology↗

CCR7 Expression Distinguishes Functionally Distinct pTfh1 Subsets with Roles in Malaria-Specific Immunity

Antibodies induced by infection or vaccination are essential mediators of protection. Induction of these protective responses is mediated by T-follicular CD4 T (Tfh) cells, and targeting these cells may be a strategy to boost antibody mediate protection. In humans, Tfh cells are analysed based on expression of CXCR3 and CCR6, with different subsets of Tfh (Tfh1, Tfh2, Tfh17) associated with antibody induction in a context-dependent manner. Here we dissected Tfh cells heterogeneity in healthy donors and individuals during controlled human malaria infection using scRNAseq. We identified two distinct Tfh1-like subsets with functional relevance, defined based on CCR7 expression. CCR7neg Tfh1 cells express markers of cytotoxicity, while CCR7pos Tfh1 cells produce reduced inflammatory cytokines and similar IL-21 resulting in unique cytokine milieu. In controlled human malaria infection, both CCR7pos and CCR7neg Tfh1, along with Tfh2 cells, clonally expanded and were transcriptionally and phenotypically activated. However, only CCR7pos Tfh1 and Tfh2 cells associated with antibody development, suggesting a role for both these Tfh subsets in promoting humoral immunity to malaria. Data identify specific protective Tfh subsets that can be targeted to improve antibody mediated protection to malaria induced, and provide a frame work to dissect the role of Tfh subsets in other disease contexts.

immunology↗