Biology subjects

White, I.

Publications and source records attributed to White, I..

3 recordsLinked to original sources

bioRxiv2022

Human intestinal epithelial cells can internalize luminal fungi via LC3-associated phagocytosis

Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the {beta}-glucan receptor Dectin-1, and respond to commensal fungi and {beta}-glucans. In phagocytes, Dectin-1 mediates LC3 associated phagocytosis (LAP) utilizing autophagy components to process extracellular cargo. Dectin-1 can mediate phagocytosis of {beta}-glucan-containing particles by non-phagocytic cells. We aimed to determine whether human IECs phagocytose {beta}-glucan-containing fungal particles via LAP. Zymosan ({beta}-glucan particle) and Heat-killed and UV inactivated C. albicans were phagocytosed by monolayers of human colonic (n=18) and ileal (n=4) organoids and IEC lines. LAP was identified by LC3 and Rubicon recruitment to phagosomes and lysosomal processing of internalized particles was demonstrated by co-localization with lysosomal dyes and LAMP2. Phagocytosis was significantly diminished by blockade of Dectin-1, actin polymerization and NAPDH oxidases. Our results show that human IECs sense luminal fungal particles and internalize them via LAP. This novel mechanism of luminal sampling suggests that IECs may contribute to the maintenance of mucosal tolerance towards commensal fungi.

immunology↗

bioRxiv2019

Conduit integrity is compromised during acute lymph node expansion

Lymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis. HighlightsO_LIFRCs use polarized microtubule networks to guide matrix deposition C_LIO_LICLEC-2/PDPN controls matrix production at transcriptional and post-transcriptional levels C_LIO_LIFRCs halt matrix production and decouple from conduits during acute LN expansion C_LIO_LIConduits leak soluble antigen during acute LN expansion C_LI

immunology↗

bioRxiv2018

Effect of Heterogeneity in Recombination Rate on Variation in Realised Relationship

Individuals of specified pedigree relationship vary in the proportion of the genome they share identical by descent, i.e. in their realised or actual relationship. Basing predictions of the variance in realised relationship solely on the proportion of the map length shared implicitly assumes that both recombination rate and genetic information are uniformly distributed along the genome, ignoring the possible existence of recombination hotspots, and failing to distinguish between coding and non-coding sequences. In this paper we quantify the effects of heterogeneity in recombination rate at broad and fine scale levels on the variation in realised relationship. A chromosome with variable recombination rate usually shows more variance in realised relationship than does one having the same map length with constant recombination rate, especially if recombination rates are higher towards chromosome ends. Reductions in variance can also be found, and the overall pattern of change is quite complex. In general, local (fine-scale) variation in recombination rate, e.g. hotspots, has a small influence on the variance in realised relationship. Differences in rates across longer regions and between chromosome ends can increase or decrease the variance in realised relationship, depending on the genomic architecture.

genetics↗