Murine inflammatory caspase-11 has an important role in intestinal epithelial inflammation and barrier function. Activation of the non-canonical inflammasome, mediated by caspase-11, serves as a regulatory pathway for the production of the pro-inflammatory cytokines IL-1β and IL-18, and has a key role in pyroptotic cell death. We have previously demonstrated a protective role for caspase-11 during dextran sulphate sodium (DSS)-induced colitis, however the importance of caspase-11 during colorectal tumour development remains unclear. Here, we show that Casp11 −/− mice are highly susceptible to the azoxymethane (AOM)-DSS model of colitis-associated cancer (CAC), compared to their wild type (WT) littermates. We show that deficient IL-18 production occurs at initial inflammation stages of disease, and that IL-1β production is more significantly impaired in Casp11 −/− colons during established CAC. We identify defective STAT1 activation in Casp11 −/− colons during disease progression, and show that IL-1β signalling induces caspase-11 expression and STAT1 activation in primary murine macrophages and intestinal epithelial cells. These findings uncover an anti-tumour role for the caspase-11 and the non-canonical inflammasome during CAC, and suggest a critical role for caspase-11, linking IL-1β and STAT1 signalling pathways.

Barrett's esophagus (BE) is an inflammatory condition and a neoplastic precursor to esophageal adenocarcinoma (EAC). Inflammasome signaling, which contributes to acute and chronic inflammation, results in caspase-1 activation leading to the secretion of IL-1β and IL-18, and inflammatory cell death (pyroptosis). This study aimed to characterize caspase-1 expression, and its functional importance, during disease progression to BE and EAC.Three models of disease progression (Normal-BE-EAC) were employed to profile caspase-1 expression: (1) a human esophageal cell line model; (2) a murine model of BE; and (3) resected tissue from BE-associated EAC patients. BE patient biopsies and murine BE organoids were cultured ex-vivo in the presence of a caspase-1 inhibitor, to determine the importance of caspase-1 for inflammatory cytokine and chemokine secretion. Epithelial caspase-1 expression levels were significantly enhanced in BE (p<0.01). In contrast, stromal caspase-1 levels correlated with histological inflammation scores during disease progression (p<0.05). Elevated secretion of IL-1β from BE explanted tissue, compared to adjacent normal tissue (p<0.01), confirmed enhanced activity of caspase-1 in BE tissue.Caspase-1 inhibition in LPS-stimulated murine BE organoids caused a significant reduction in IL-1β (p<0.01) and CXCL1 (p<0.05) secretion, confirming the importance of caspase-1 in the production of cytokines and chemokines associated with disease progression from BE to EAC.Targeting caspase-1 activity in BE patients should therefore be tested as a novel strategy to prevent inflammatory complications associated with disease progression.

Ireland has a rich history of public engagement with science and the growing number of national citizen science initiatives is in keeping with developments seen in other European countries. This paper explores several aspects of citizen science in Ireland, in order to assess its development and to better understand potential opportunities for the field. An introduction to the roots of citizen science in Ireland’s past, from the first methodical observations of natural phenomena carried out at monastic settlements up to present day projects monitoring environmental change and biodiversity, is presented along with an overview of the current national citizen science projects running in the country. This cataloging of contemporary citizen science will be compared to the awareness of citizen science in the Irish education system at primary, post-primary, and university level. These measures of progress will be considered in the changing context of international citizen science funding and available support, such as the European Citizen Science Association and the EU-Citizen.Science platform. Citizen science in Ireland is at a critical point. If citizen science is embraced as a truly social and participatory innovation, Ireland has the chance to not only dramatically improve its citizen science output, but to also become a model of best practice for countries at similar stages of citizen science development.

Data availability statement No datasets were generated or analyzed during this current study.

Chronic inflammation plays an important role in the pathogenesis of oesophageal adenocarcinoma (EAC) and its only known precursor, Barrett’s oesophagus (BE). Recent studies have shown that oesophageal TLR2 levels increase from normal epithelium towards EAC. TLR2 signalling is therefore likely to be important during EAC development and progression, which requires an inflammatory microenvironment. Here, we show that, in response to TLR2 stimulation, BE organoids and early-stage EAC cells secrete pro-inflammatory cytokines and chemokines which recruit macrophages to the tumour site. Factors secreted from TLR2-stimulated EAC cells are shown to subsequently activate TLR2 on naïve macrophages, priming them for inflammasome activation and inducing their differentiation to an M2/TAM-like phenotype. We identify the endogenous TLR2 ligand, HMGB1, as the factor secreted from EAC cells responsible for the observed TLR2-mediated effects on macrophages. Our results indicate that HMGB1 signalling between EAC cells and macrophages creates an inflammatory tumour microenvironment to facilitate EAC progression. In addition to identifying HMGB1 as a potential target for early-stage EAC treatment, our data suggest that blocking TLR2 signalling represents a mechanism to limit HMGB1 release, inflammatory cell infiltration and inflammation during EAC progression.