Project description:We show here the transcriptional response in the liver of pigs infected or not with Ascaris suum, fed either a control pr a PAC-enriched diet
Project description:We show here the transcriptional response in the lung of pigs infected or not with Ascaris suum, fed either a control pr a PAC-enriched diet
Project description:We show here the transcriptional response in the intestine of pigs infected or not with Ascaris suum, fed either a control pr a PAC-enriched diet
Project description:Ascariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected with Ascaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school aged children but then declines with age. The cause of age-dependent Ascaris worm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site for Ascaris infection. Following oral ingestion of Ascaris eggs, larvae use AMCase secreted by gastric chief cells and acid secreted by gastric parietal cells to hatch. Once hatched, larvae translocate across the gastric mucosa to initiate the larval migratory cycle. However, inducing mucosal injury with administration of Tamoxifen induces mucosa cellular changes that impairs Ascaris hatching and reduces larval translocation across the gastric mucosa. In this study we established a repeated Ascaris suum challenge mouse model and evaluated if repeated Ascaris challenge also lead to cellular changes in the gastric mucosal barrier. We found that repeated Ascaris challenge caused cellular changes in the gastric mucosa which reduced worm intensity in the liver independent of the adaptive immune response. Thus, in endemic regions, where individuals experience recurrent infection throughout their lives, gastric cellular changes may be a key mechanism leading to the observed age-dependent Ascaris worm intensity changes from childhood to adulthood.
Project description:The highly prevalent gut helminth, Ascaris suum, compromise pigs health and reduce farm productivity worldwide. The closely related human parasite, A. lumbricoides, infects more than 800 million people and causes approximately 1.31 million disability-adjusted life years. The humaninfections are often chronic by nature and the parasites have a profound ability to modulate their hosts immune responses. This study provides the first in-depth characterization of extracellular vesicles (EVs) from different developmental stages and body parts of A. suum and their potential role in the host-parasite interplay. The release of EVs during the third larval stage (L3), L4 and adults was demonstrated by Transmission Electron Microscopy, and the uptake of EVs from adult A. suum in intestinal epithelial cells followed by accumulation of RNA in the nucleus by confocal microscopy. Next Generation Sequencing of EV-derived mi/m?RNA identified a number of micro(mi)RNAs from the different A. suum life stages and body parts and potential transcripts of potential host immune targets, such as IL-13, IL-25 and IL-33, were identified. Proteomics of EVs identified several proteins with immunomodulatory properties and other proteins previously shown to be associated with parasite EVs. Furthermore, EVs from A. suum body fluid stimulated the production of the pro-inflammatory cytokines IL-6 and TNF-α in dendritic cells in vitro. Taken together, these results suggest that A. suum EVs and their cargo may play a role in host-parasite interactions. This knowledge may pave the way for novel strategies for helminth infection control and knowledge of their immune modulatory role.
Project description:In 2010, Ascaris caused 819 million infections worldwide. The impact on children is particularly severe, causing growth retardation and detrimental effects on cognitive development. Transmission is linked to unhygienic defecation habits, making ascariasis a disease of poverty. The WHO recognises it as one of the world's 17 neglected tropical diseases. Ascariasis is also an important parasite of pigs with economic implications including liver condemnation. Intriguingly some people (and pigs) are very heavily infected with Ascaris whereas others are not and this research aims to understand the factors that give rise to this difference and ultimately resistance to Ascaris itself. In our study we performed label free quantitative proteomics on livers of day four post infection C57BL/6J and CBA/Ca mice with and without Ascaris infection to identify proteins changes potentially linked to both resistance and susceptibility amongst the two strains, respectively. In addition tio major intrinsic differences between the two strains signatures of a differential immune response and direct modulation of host processes by the nematode were resolved.
