Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells.

Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T-cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T-cell exhaustion markers phenotypically. T-cell lineage (CD3, CD4, and CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, and 2B4), and senescence (CD28-) markers were assessed. Dimensionality reduction methods revealed increased PD1, TIM3, and LAG3 expression in malaria-exposed individuals. Manual gating confirmed significantly higher frequencies of PD1+CD4+ and CD4+, CD8+, and double-negative (DN) T cells expressing TIM3 in malaria-exposed individuals. Increased frequencies of T cells co-expressing multiple markers were also found in malaria-exposed individuals. T-cell data were analyzed with B-cell populations from a previous study where we reported an alteration of B-cell subsets, including increased frequencies of atypical memory B cells (aMBC) and reduction in marginal zone (MZ-like) B cells during malaria exposure. Frequencies of aMBC subsets and MZ-like B cells expressing CD95+ had significant positive correlations with CD28+PD1+TIM3+CD4+ and DN T cells and CD28+TIM3+2B4+CD8+ T cells. Frequencies of aMBC, known to associate with malaria anemia, were inversely correlated with hemoglobin levels in malaria-exposed women. Similarly, inverse correlations with hemoglobin levels were found for TIM3+CD8+ and CD28+PD1+TIM3+CD4+ T cells. Our findings provide further insights into the effects of chronic malaria exposure on circulating B- and T-cell populations, which could impact immunity and responses to vaccination.

Clinical recrudescence of chronic untreated P. malariae infection after BNT162b2 CoVID-19 vaccine.

We described a case of clinical reactivation of chronic P. malariae infection following CoVID-19 vaccination with BNT162b2 (Pifzer-Biontech CoVID-19 vaccine) in a 48-year old Italian man.The patient came to our attention for fever of unknown origin show a quartan pattern (every third day) associated to splenomegaly, the onset of the fever occurred one month after CoVID-19 vaccination with BNT162b2. P. malariae was diagnosed using Carestart™ malaria rapid test and Polymerase-Chain Reaction. Post-vaccine transient reduction of immune reactivity is described in literature, although the mechanism is unknown.

The Contribution of Co-signaling Pathways to Anti-malarial T Cell Immunity.

Plasmodium spp., the causative agent of malaria, caused 212 million infections in 2016 with 445,000 deaths, mostly in children. Adults acquire enough immunity to prevent clinical symptoms but never develop sterile immunity. The only vaccine for malaria, RTS,S, shows promising protection of a limited duration against clinical malaria in infants but no significant protection against severe disease. There is now abundant evidence that T cell functions are inhibited during malaria, which may explain why vaccine are not efficacious. Studies have now clearly shown that T cell immunity against malaria is subdued by multiple the immune regulatory receptors, in particular, by programmed cell-death-1 (PD-1). Given there is an urgent need for an efficacious malarial treatment, compounded with growing drug resistance, a better understanding of malarial immunity is essential. This review will examine molecular signals that affect T cell-mediated immunity against malaria.