The Impact of Malaria-Induced Neutrophil Subset Shift and a Link to Burkitt Lymphoma

Abstract

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that remains a leading cause of childhood cancer mortality in sub-Saharan Africa. Although the epidemiological link between Plasmodium falciparum (Pf) malaria and BL has been established, our understanding of the underlying immunological mechanisms conducive to tumorigenesis is incomplete. To address a noted gap in our knowledge of the immune landscape, we profiled neutrophil subsets from children with different exposure histories to Pf-malaria and children diagnosed with BL from Western Kenya, along with healthy malaria-naive Kenyan adults. Using multiparameter flow cytometry, we characterized neutrophils by expression of CD15, CD16, CD10, CD11b, CD182, CD184, and CD62L and found that malaria-exposed children exhibited increased frequencies of aged neutrophil subsets, accompanied by a reduction in the mature subset frequencies compared to malaria-naive children. Malaria-exposed children also had neutrophil profiles that closely resembled those seen in the adults. Notably, a positive correlation (rs = 0.7; p < 0.0001) was observed in immature neutrophils between malaria-exposed healthy and BL children, indicating a similar expansion pattern of this subset in both groups. This finding suggests a malaria-driven expansion of the immature subset, potentially promoting a permissive environment for BL. Our data suggests that the observed shift in neutrophil profiles could contribute to the malaria-induced immunopathology associated with BL Visual abstractCreated in BioRender. Forconi, C. (2025) https://BioRender.com/oz60qvq O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/681992v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1640dc4org.highwire.dtl.DTLVardef@1c3e794org.highwire.dtl.DTLVardef@98bf12org.highwire.dtl.DTLVardef@2851b8_HPS_FORMAT_FIGEXP M_FIG C_FIG