Biology subjects

Babatunde, K. A.

Publications and source records attributed to Babatunde, K. A..

4 recordsLinked to original sources

bioRxiv2025

Plasmodium falciparum subverts neutrophil function via host miR-451a loaded extracellular vesicles driving bacterial superinfection susceptibility

Malaria caused by Plasmodium falciparum (Pf) compromise innate immunity, yet the underlying mechanisms remain elusive. The immune dysregulation caused by the parasite may lead to bacterial superinfections and increase mortality. We reveal that Pf exploits extracellular vesicles (EVs) secreted by infected red blood cells (iRBC-EVs) to deliver host-derived miR451a to human neutrophils, impairing their antimicrobial defences. Neutrophil phagocytosis of iRBC-EVs suppresses reactive oxygen species (ROS) production and compromised microbicidal activity against Salmonella typhimurium. Microfluidic assays show that miR451a transfer significantly disrupts neutrophil chemotaxis and swarming upon microbial challenge. Transcriptomic profiling indicates that EVs and miR451a reprogram neutrophil gene expression, notably upregulating ferroptosis-related genes, suggesting a role in further impairing immune responses. We have uncovered a novel mechanism of iRBC-EVs-induced neutrophil immune suppression and provide insights into increased susceptibility to bacterial superinfections in malaria. These findings have implications for therapeutic strategies aimed at mitigating bacterial superinfections and sepsis in malaria-endemic regions.

immunology↗

bioRxiv2024

A microphysiological system of sterile injury demonstrates neutrophil reverse migration via macrophage-derived extracellular vesicle crosstalk.

Persistent neutrophilic inflammation can lead to tissue damage and chronic inflammation, contributing to non-healing wounds. The resolution phase of neutrophilic inflammation is critical to preventing tissue damage, as observed in diseases characterized by influx of neutrophils such as atherosclerosis and non-healing wounds. Animal models have provided insight into resolution of neutrophilic inflammation via efferocytosis and reverse migration (rM); however, species-specific differences and complexity of innate immune responses make translation to humans challenging. Thus, there is a need for in vitro systems that can elucidate mechanisms of resolution of human neutrophilic inflammation. Here, we developed a human microphysiological system (MPS) to mimic an inflammatory sterile injury (SI) microenvironment to study the role of macrophage derived extracellular vesicles (M-EVs) in determining the resolution of inflammation via neutrophil rM. The MPS integrates a human umbilical vein endothelial cell (HUVEC) lined lumen, injury site spheroid, human neutrophils, macrophages and macrophage derived EVs to investigate the role of M-EVs in neutrophil rM in vitro. The key features of the MPS enabled us to demonstrate that EVs derived from macrophage subsets modulate migratory behavior in primary neutrophils differently in specific inflammatory microenvironments. Importantly, we identified a new mechanism underlying neutrophil rM via M-EV, where neutrophils exposed to M2-EV-derived IL-8 migrate away from the SI site upon reaching the site, using the SI MPS. Overall, our SI MPS system demonstrates a reverse migratory pattern in human primary neutrophils, advancing the study of the resolution of inflammation via M-EVs.

immunology↗

bioRxiv2023

Naive primary neutrophils play a dual role in the tumor microenvironment

The tumor microenvironment (TME) is characterized by a network of cancer cells, recruited immune cells and extracellular matrix (ECM) in a hypoxic microenvironment. However, the specific role of neutrophils during tumor development, and their interactions with other immune cells is still not well understood. Thus, there is a need to investigate the interaction between primary neutrophils and natural killer cells and the resulting effects on tumor development. Here we use both standard well plate culture and an under oil microfluidic (UOM) assay with an integrated extracellular cell matrix (ECM) bridge to elucidate how naive primary neutrophils respond to both patient derived tumor cells and tumor cell lines. Our data demonstrated that both patient derived head and neck squamous cell carcinoma (HNSCC) tumor cells and MDA-MB-231 breast cancer cells trigger cluster formation in neutrophils, and the swarm of neutrophils restricts tumor invasion through the generation of reactive oxygen species (ROS) and neutrophil extracellular trap (NETs) release within the neutrophil cluster. However, we also observed that the presence of neutrophils downregulates granzyme B in NK-92 cells and the resulting NETs can obstruct NK cells from penetrating the tumor mass in vitro suggesting a dual role for neutrophils in the TME. Further, using label-free optical metabolic imaging (OMI) we observed changes in the metabolic activities of primary neutrophils during the different swarming phases when challenged with tumor cells. Finally, our data demonstrates that neutrophils in direct contact, or in close proximity, with tumor cells exhibit greater metabolic activities (lower nicotinamide adenine dinucleotide phosphate (NAD(P)H) mean lifetime) compared to non-contact neutrophils.

cell biology↗

bioRxiv2019

Chemotaxis and swarming in differentiated HL60 neutrophil-like cells

Human leukemia cell line (HL-60) is an alternative to primary neutrophils in research studies. However, because HL-60 cells proliferate in an incompletely differentiated state, they must undergo differentiation before they acquire the functional properties of neutrophils. Here we provide evidence of swarming and chemotaxis in HL-60 neutrophil-like cells using precision microfluidic assays. We found that dimethyl sulfoxide (DMSO) differentiated HL-60 cells have larger size, increased length, and lower ability to squeeze through narrow channels compared to primary neutrophils. They migrate through tapered microfluidic channels slower than primary neutrophils, but faster than HL60s differentiated by other protocols, e.g. using all-trans retinoic acid. We found that differentiated HL-60 can swarm toward zymosan particle clusters, though they display disorganized migratory patterns and produce swarms of smaller size compared to primary neutrophils.

cell biology↗