Biology subjects

Forconi, C. S.

Publications and source records attributed to Forconi, C. S..

3 recordsLinked to original sources

bioRxiv2025

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

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

immunology↗

bioRxiv2024

T follicular helper cell profiles differ by malaria antigen and for children compared to adults

BackgroundCirculating T-follicular helper (cTFH) cells have the potential to provide an additional correlate of protection against Plasmodium falciparum (Pf) as they are essential to promote B-cell production of long-lasting antibodies. Assessing the specificity of cTFH subsets to individual malaria antigens is vital to understanding the variation observed in antibody responses and identifying promising malaria vaccine candidates. MethodsUsing spectral flow cytometry and unbiased clustering analysis, we assessed antigen-specific cTFH cell recall responses in vitro to malaria vaccine candidates Pf-schizont egress antigen-1 (PfSEA-1A) and Pf-glutamic acid-rich protein (PfGARP) within a cross-section of children and adults living in a malaria-holoendemic region of western Kenya. FindingsIn children, a broad array of cTFH subsets (defined by cytokine and transcription factor expression) were reactive to both malaria antigens, PfSEA-1A and PfGARP, while adults had a narrow profile centering on cTFH17- and cTFH1/17-like subsets following stimulation with PfGARP only. InterpretationBecause TFH17 cells are involved in the maintenance of memory antibody responses within the context of parasitic infections, our results suggest that PfGARP might generate longer-lived antibody responses compared to PfSEA-1A. These findings have intriguing implications for evaluating malaria vaccine candidates as they highlight the importance of including cTFH profiles when assessing interdependent correlates of protective immunity.

immunology↗

bioRxiv2023

Epigenetic regulation of innate immune genes and enhanced interleukin-10 expression underlie chronic subclinical Plasmodium chabaudi infection

Subclinical (asymptomatic) parasitemia is very common amongst Plasmodium-infected individuals. The immunological mechanisms underlying subclinical parasitemia remain elusive. We investigated the immune regulatory mechanisms behind chronic asymptomatic Plasmodium infection using mice lacking humoral immunity ({micro}MT-/- mice). {micro}MT-/- mice became chronically infected, despite lacking outward signs of disease, and exhibited increased macrophage numbers, decreased dendritic and CD4 cells, massive hemozoin accumulation in the spleen and bone marrow, and inadequate hematopoiesis. These changes were accompanied by high circulating levels of interleukin-10 (IL-10), enhanced chromatin accessibility of the STAT3 promoter, and enhanced STAT3 binding to the IL-10 promoter in macrophages. Inhibition of IL-10 signaling, despite promoting parasite clearance, resulted in a proinflammatory response, weight loss, and mortality. These results suggest that epigenetic changes induced by chronic P. chabaudi infection lead to high levels of circulating IL-10, protecting chronically infected mice against an excessive inflammatory response to high levels of blood-stage parasites. Author summaryMalaria is a life-threatening disease with a range of symptoms, and it is induced in humans by infections with different species of Plasmodium. Highly prevalent in endemic regions, asymptomatic Plasmodium infections are related to long-term exposure to the parasite due to multiple infections and have been demonstrated in human and mouse studies to be associated with elevated levels of IL-10. However, how IL-10 levels remain elevated in the circulation in individuals over the long term has not been determined. We used a mouse model of chronic asymptomatic Plasmodium infection to investigate the mechanisms by which IL-10 levels are elevated during chronic asymptomatic infection. Our results show that epigenetic changes in immune genes of myeloid origin could be responsible for the elevated levels of IL-10, and that IL-10 signaling protected chronically infected mice from a severe inflammatory response induced by the infection.

immunology↗