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

Mitchell, RA; Ubillos, I; Requena, P; Campo, JJ; Ome-Kaius, M; Hanieh, S; Umbers, A; Samol, P; Barrios, D; Jim&#233;nez, A; Bardaj&#237;, A; Mueller, I; Men&#233;ndez, C; Rogerson, S; Doba&#241;o, C; Moncunill, G

Author(s): Mitchell, RA; Ubillos, I; Requena, P; Campo, JJ; Ome-Kaius, M; Hanieh, S; Umbers, A; Samol, P; Barrios, D; Jiménez, A; Bardají, A; Mueller, I; Menéndez, C; Rogerson, S; Dobaño, C; Moncunill, G;
Details: Publication Year 2024-02-22,Volume 216,Issue #2,Page 172-191
Journal Title: Clinical & Experimental Immunology
Abstract: 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, CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, 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-like (MZ-like) B cells during malaria exposure. Frequencies of aMBC subsets and MZ-like B cells expressing CD95+ had significant positive correlations with CD4+ and DN T cells expressing CD28+PD1+TIM3+ 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.
Publisher: Oxford Academic
Keywords: B-cell; Chronic malaria; T-cell; exhaustion; tolerance
Research Division(s): Population Health And Immunity
PubMed ID: 38387476
Publisher's Version: https://doi.org/10.1093/cei/uxae015
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:16:14

Last Modified: 2024-05-09 09:00:53