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The impact of malaria-induced neutrophil subset shift and a link to Burkitt lymphoma
Sharon Akinyi Okoth1,2, Ronald K Tonui3,4, Titus K Maina5
1Department of Zoology, Maseno University, Maseno, Kenya.
Insights
Plasmodium falciparum malaria exposure in children is linked to an expansion of immature neutrophils, a subset known to promote tumors. This finding may explain how malaria contributes to Burkitt lymphoma development.
Area of Science:
- Immunology
- Oncology
- Infectious Diseases
Background:
- Burkitt lymphoma (BL) is a significant cause of childhood cancer mortality in sub-Saharan Africa.
- The link between Plasmodium falciparum (Pf) malaria and BL is known, but the immunological mechanisms are unclear.
- Neutrophils play a role in immune responses and cancer development.
Purpose of the Study:
- To investigate neutrophil subset profiles in children with varying Plasmodium falciparum malaria exposure.
- To compare neutrophil subsets between healthy children, children with Burkitt lymphoma, and healthy adults.
- To identify potential immunological links between malaria exposure and Burkitt lymphoma pathogenesis.
Main Methods:
- Prospective study involving children from Western Kenya with different Pf-malaria exposure histories and BL diagnoses.
- Utilized multiparameter flow cytometry to characterize neutrophil subsets.
- Analyzed neutrophil expression of CD15, CD16, CD10, CD11b, CD182, CD184, and CD62L.
Main Results:
- Malaria-exposed children showed increased frequencies of aged neutrophil subsets and decreased mature active subsets compared to low-exposed children.
- A significant positive correlation was found in immature neutrophils between malaria-exposed healthy children and those with BL.
- Findings suggest a malaria-associated expansion of the immature neutrophil subset.
Conclusions:
- Malaria exposure is associated with a shift in neutrophil profiles, including an expansion of immature subsets.
- Immature neutrophils may possess tumor-promoting functions, potentially contributing to a permissive environment for BL.
- These immunological changes linked to malaria could be a key factor in Burkitt lymphoma development.
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 conducted a prospective study to profile neutrophil subsets from children with different exposure histories to Pf-malaria and children diagnosed with BL from Western Kenya, along with healthy malaria low-exposed 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 active subset frequencies compared to malaria low-exposed children. Notably, a positive correlation (rs = 0.7; p < 0.0001) was observed in immature neutrophils between malaria-exposed healthy and BL children, revealing a possible similar expansion of this subset in both groups. These findings suggest a malaria-associated expansion of the immature neutrophil subset. While functional assays were not performed in this study, previous reports indicate that immature neutrophils can exhibit tumor-promoting functions. Therefore, the observed shift in neutrophil profiles may reflect phenotypic changes associated with malaria exposure that could contribute to a permissive environment for BL.
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