ORCID Profile
0000-0002-4628-7890
Current Organisation
Monash University
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Publisher: Rockefeller University Press
Date: 15-11-2021
DOI: 10.1084/JEM.20211140
Abstract: Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations. In vitro, using small intestinal organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked the effects of IL-4/13, inhibiting tuft and goblet cell gene expression and expansion, and inducing spheroid growth characteristic of fetal epithelium and homeostatic repair. Similar outcomes were seen in organoids exposed to parasite larvae. In vivo, H. polygyrus infection inhibited tuft cell responses to heterologous Nippostrongylus brasiliensis infection or succinate, and HpES also reduced succinate-stimulated tuft cell expansion. Our results demonstrate that helminth parasites reshape their intestinal environment in a novel strategy for undermining the host protective response.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 25-11-2014
DOI: 10.1038/NCOMMS6488
Abstract: In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus , which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. Microarray analysis of mouse cells incubated with nematode exosomes in vitro identifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematode Litomosoides sigmodontis in the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.
Publisher: Elsevier BV
Date: 05-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-05-2020
DOI: 10.20900/IMMUNOMETAB20200018
Abstract: Type 2 immune cells are key to the maintenance of healthy adipose tissue, however the cues responsible for the establishment and maintenance of adipose type two immune cells remain unclear. Rana et al. report a specialized stromal cell produces interleukin-33 (IL-33) that activates group 2 innate lymphoid cells (ILC2s). Activated ILC2s in turn produce type two cytokines that elicit further IL-33 production by the stroma in a positive feedback loop that maintains the type 2 immune cell network within visceral adipose tissue (VAT).
Publisher: Elsevier BV
Date: 10-2015
Publisher: Elsevier BV
Date: 07-2016
Publisher: MyJove Corporation
Date: 06-04-2015
DOI: 10.3791/52412
Publisher: Wiley
Date: 2016
DOI: 10.3402/JEV.V5.30741
Abstract: Extracellular vesicles (EVs) mediate communication between cells and organisms across all 3 kingdoms of life. Several reports have demonstrated that EVs can transfer molecules between phylogenetically erse species and can be used by parasites to alter the properties of the host environment. Whilst the concept of vesicle secretion and uptake is broad reaching, the molecular composition of these complexes is expected to be erse based on the physiology and environmental niche of different organisms. Exosomes are one class of EVs originally defined based on their endocytic origin, as these derive from multivesicular bodies that then fuse with the plasma membrane releasing them into the extracellular environment. The term exosome has also been used to describe any small EVs recovered by high-speed ultracentrifugation, irrespective of origin since this is not always well characterized. Here, we use comparative global lipidomic analysis to examine the composition of EVs, which we term exosomes, that are secreted by the gastrointestinal nematode, Heligmosomoides polygyrus, in relation to exosomes secreted by cells of its murine host. Ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) analysis reveals a 9- to 62-fold enrichment of plasmalogens, as well as other classes of ether glycerophospholipids, along with a relative lack of cholesterol and sphingomyelin (SM) in the nematode exosomes compared with those secreted by murine cells. Biophysical analyses of the membrane dynamics of these exosomes demonstrate increased rigidity in those from the nematode, and parallel studies with synthetic vesicles support a role of plasmalogens in stabilizing the membrane structure. These results suggest that nematodes can maintain exosome membrane structure and integrity through increased plasmalogens, compensating for diminished levels of other lipids, including cholesterol and SM. This work also illuminates the prevalence of plasmalogens in some EVs, which has not been widely reported and could have implications for the biochemical or immunomodulatory properties of EVs. Further comparative analyses such as those described here will shed light on ersity in the molecular properties of EVs that enable them to function in cross-species communication.
Publisher: Frontiers Media SA
Date: 07-05-2019
Publisher: Springer Science and Business Media LLC
Date: 22-10-2015
DOI: 10.1038/NCOMMS9772
Abstract: Nature Communications 5: Article number: 5488 (2014) Published: 25 November 2014 Updated: 22 October 2015. The affiliation details for Mark Blaxter are incorrect in this Article. The correct affiliation details for this author are given below: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK.
Publisher: Wiley
Date: 03-05-2020
DOI: 10.1111/PIM.12717
Publisher: Wiley
Date: 25-05-2020
DOI: 10.1111/PIM.12728
Publisher: Springer Science and Business Media LLC
Date: 17-06-2019
Publisher: Cold Spring Harbor Laboratory
Date: 02-2021
DOI: 10.1101/2021.01.30.428930
Abstract: Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil recruitment to this organ has long remained enigmatic. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine. The microbiota is a critical regulator of eosinophil activation and turnover Eosinophils uphold intestinal barrier integrity following microbial colonization Loss of eosinophils at steady-state results in increased villous blunting and altered intestinal motility
Publisher: Wiley
Date: 2019
DOI: 10.1002/CTI2.1089
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 09-2020
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gillian Coakley.