Biology subjects

Wilson, H. L.

Publications and source records attributed to Wilson, H. L..

4 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↗

bioRxiv2026

Fisetin-mediated MYC restoration improves age-associated decline in macrophage function

Immune decline in older adults is associated with increased susceptibility to infection and chronic inflammatory diseases. Macrophages are critical innate immune cells that show reduced capacity for phagocytosis and migration with age. Our previous work shows that reduced levels of MYC and USF1 transcription factors are drivers of macrophage age-related functional decline. Here we show that macrophage-specific Myc overexpression improves macrophage migration and, more importantly, is able to improve physical performance at older age in Drosophila, while lifespan remains unaffected. Treatment of human primary macrophages from older individuals with the geroprotective supplement fisetin reverses the decline in MYC expression and improves phagocytosis of pathogens and cell migration functions towards levels seen in younger individuals. Mechanistically, fisetin acts via MYC, by restoring expression levels of MYC targets in human macrophages that are altered with age. Finally, fisetin feeding in older mice improves motor activity and reduces frailty, as well as restoring primary macrophage function and Myc expression in vitro. These findings reveal that restoration of MYC in macrophage ageing is responsible, at least in part, for improvement in physical performance with age and identify this pathway as a rational target to reverse age-related immune decline. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/731325v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1ab6731org.highwire.dtl.DTLVardef@3d85dorg.highwire.dtl.DTLVardef@71c2b3org.highwire.dtl.DTLVardef@a59bf3_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Ageing-related defects in macrophage function are driven by MYC and USF1 transcriptional programmes

Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related immunity changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years) compared with younger (18-30 years) donors, alongside downregulation of transcription factors MYC and USF1 with age. In MDMs from young donors, knockdown of MYC or USF1 decreased phagocytosis and chemotaxis and altered expression of genes associated with these functions, as well as adhesion and extracellular matrix remodelling. A concordant dysregulation of MYC and USF1 target genes was also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs led to an increased cell size, altered morphology and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in ageing.

immunology↗

bioRxiv2018

Macrophage Il-1beta protects against mycobacterial infection downstream of Hif-1alpha in zebrafish

Drug resistant mycobacteria are a rising problem worldwide. There is an urgent need to understand the immune response to TB to identify host targets that, if targeted therapeutically, could be used to tackle these currently untreatable infections. Here, we use an Il-1{beta} fluorescent transgenic line to show that there is an early innate immune pro-inflammatory response to well-established zebrafish models of inflammation and Mycobacterium marinum (Mm) infection. We demonstrate that host-derived hypoxia signalling, mediated by the Hif-1 transcription factor, can prime macrophages with increased levels of Il-1{beta} in the absence of infection, upregulating neutrophil antimicrobial nitric oxide production, leading to greater protection against infection. Our data link Hif-1 to proinflammatory macrophage Il-1{beta} transcription in vivo during early mycobacterial infection and importantly highlight a host protective mechanism, via antimicrobial nitric oxide, that decreases disease outcomes and that could be targeted therapeutically to stimulate the innate immune response to better deal with infections.

immunology↗