Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria

Abstract

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69+ NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4+ lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.

STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria

“…We report high plasma levels of proinflammatory cytokines and chemokines (IFNγ, TNF, IL-6, CCL2, CCL3, CCL4, CXCL10) in severe malaria patients compared to baseline uninfected follow-up, which matched that of Py infection in mice in which we could conduct a temporal analysis. Only few studies have performed functional immunophenotyping during severe human malaria [21, 25], and most of them focused on specific subsets of immune cells, namely NK cells, γδT cells and CD4 + T cells. Our study examined both myeloid and lymphoid cell compartments to provide a global analysis of blood immune leukocytes during severe human malaria.…”

“…In this context, a role for Foxp3 + CD4 + regulatory T cells (Tregs) as well as non-Foxp3 + activated/memory (CD45RO + ) CD4 + T cells in regulating malaria-induced inflammation and subsequent immunopathology is supported by many studies in human patients and in surrogate mouse models [19–24]. NK and γδ T cell activation is increased in children suffering from CM compared to other forms of malaria, as is the proportion of activated/memory T cells [25]. Inflammatory CCR2 + CD14 + monocytes mediate antibody-dependent cellular inhibition, and their higher proportion was correlated to lower blood parasitemia in acute uncomplicated malaria patients [9].…”

Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria

“…Antibodies that develop through exposure to P. falciparum play a role (3), and the involvement of different lymphocyte subsets has been implicated in both protection against, and pathogenesis of, malaria (4–6). …”

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

“…Triplicate Results from flow cytometric analysis unexpectedly revealed that 46.9% (mean, n = 15) of these CD8 mid cells expressed the prototypic NK cell maker, CD56 ( S1 Fig, cell population 9) . Abnormal lymphocyte subtypes have been previously reported in patients from malaria endemic areas [10, 36]; however, at the time of writing, this phenotype has not been reported in Haiti to the best of our knowledge, and may be unique to the study population. Both CD8 mid populations (CD56 + and CD56 - ) experienced a statistically significant rise in the percentage of positive cells in the asymptomatic patient group exposed to infected erythrocytes at the schizont stage (iRBC lysate) vs uninfected erythrocytes (uRBCs; Fig 4A and 4B).…”