Biology subjects

Ho, Y. X.

Publications and source records attributed to Ho, Y. X..

3 recordsLinked to original sources

bioRxiv2026

Macrophages use sub-micron actin ridges in phagocytosis of encapsulated fungal pathogens

Ingestion and killing of pathogens by phagocytic cells is a key aspect of animal immunity. Cryptococcus neoformans is a major pathogen of AIDS patients that has a polysaccharide capsule that is critical for virulence. Phagocytic function is necessary for normal immunity to cryptococcal infection, and we sought to determine how Cryptococcus capsule prevents phagocytosis. In doing so, we discovered a new sub-micron actin structure, the ridge, that is present on macrophages, neutrophils and amoebae. Macrophages preferentially bind cryptococci via ridges and suppression of ridges is sufficient to prevent phagocytosis. Ridges are present on macrophages in vivo and are lost in interleukin 10 stimulated macrophages. The discovery and functional description of macrophage surface ridges fills a critical gap in our understanding of how phagocytes ingest encapsulated fungal pathogens, a crucial step in treating infection.

cell biology↗

bioRxiv2024

Pulses of Class I PI3kinase activity identify the release and recapture of prey from neutrophil phagosomes

Class I PI3kinases coordinate the delivery of microbicidal effectors to the phagosome by forming the phosphoinositide lipid second messenger, phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). However, the dynamics of PIP3 in neutrophils during a bacterial infection are unknown. We have therefore developed an in vivo, live zebrafish infection model that enables visualisation of dynamic changes in Class 1 PI3kinases (PI3K) signalling on neutrophil phagosomes in real-time. We have identified that on approximately 12% of neutrophil phagosomes PHAkt-eGFP, a reporter for Class 1 PI3K signalling, re-recruits in pulsatile bursts. This phenomenon occurred on phagosomes containing structurally and morphologically distinct prey, including Staphylococcus aureus and Mycobacterium abscessus, and was dependent on the activity of the Class 1 PI3K isoform, PI3kinase {gamma}. Detailed imaging suggested that pulsing phagosomes represent neutrophils transiently reopening and reclosing phagosomes. This finding challenges the concept that phagosomes remain closed after prey engulfment and we propose that neutrophils occasionally use this alternative pathway of phagosome maturation to release phagosome contents and/or to restart phagosome maturation if digestion has stalled.

cell biology↗

bioRxiv2021

Multi-modal imaging reveals dynamic interactions of Staphylococcus aureus within human neutrophils

Staphylococcus aureus is an important human pathogen that causes a wide range of infections. Neutrophils are an essential component of our innate immune system and understanding S. aureus-neutrophil interactions on a sub-cellular level is crucial to developing new therapeutic strategies to promote immunity during S. aureus infections. To this end we have developed a multi-modal imaging platform capable of following host-pathogen processes in biological systems, this is achieved by switching imaging modalities between a low photo-toxicity and low resolution imaging modality through an increasing illumination intensity to achieve live super-resolution imaging. This novel imaging platform was applied to the study of human neutrophils infected by S. aureus. We show that we can image different infection stages of S. aureus in live neutrophils with super resolution microscopy. We see evidence of binary fission occurring in intracellular S. aureus within a neutrophil.

biophysics↗