Characterising the Mucosal and Systemic Immune Responses to Experimental Human Hookworm Infection

The mucosal cytokine response of healthy humans to parasitic helminths has never been reported. We investigated the systemic and mucosal cytokine responses to hookworm infection in experimentally infected, previously hookworm naive individuals from non-endemic areas. We collected both peripheral blood and duodenal biopsies to assess the systemic immune response, as well as the response at the site of adult worm establishment. Our results show that experimental hookworm infection leads to a strong systemic and mucosal Th2 (IL-4, IL-5, IL-9 and IL-13) and regulatory (IL-10 and TGF-β) response, with some evidence of a Th1 (IFN-γ and IL-2) response. Despite upregulation after patency of both IL-15 and ALDH1A2, a known Th17-inducing combination in inflammatory diseases, we saw no evidence of a Th17 (IL-17) response. Moreover, we observed strong suppression of mucosal IL-23 and upregulation of IL-22 during established hookworm infection, suggesting a potential mechanism by which Th17 responses are suppressed, and highlighting the potential that hookworms and their secreted proteins offer as therapeutics for human inflammatory diseases

TLR1-induced chemokine production is critical for mucosal immunity against Yersinia enterocolitica

Our gastrointestinal tract is a portal of entry for a number of bacteria and viruses. Thus, this tissue must develop ways to induce antigen-specific T cell and antibody responses quickly. Intestinal epithelial cells are a central player in barrier function and also in communicating signals from invading pathogens to the underlying immune tissue. Here we demonstrate that activation of Toll-like receptor 1 (TLR1) in the epithelium leads to the upregulation of the chemokine CCL20 during oral infection with Yersinia enterocolitica. Further, both neutralization of CCL20 using polyclonal antibody treatment and deletion of TLR1 resulted in a defect in CCR6+ dendritic cells (DCs), which produce innate cytokines that help to induce anti-Yersinia-specific T helper 17 (T(H)17) cells and IgA production. These data demonstrate a novel role for TLR1 signaling in the intestinal epithelium and demonstrate that together TLR1 and CCL20 are critical mediators of T(H)17 immunity through the activation and recruitment of DCs

A Palaeoproterozoic tectono-magmatic lull as a potential trigger for the supercontinent cycle

© 2018 © Macmillan Publishers Limited, part of Springer Nature 2018 The geologic record exhibits periods of active and quiescent geologic processes, including magmatism, metamorphism and mineralization. This apparent episodicity has been ascribed either to bias in the geologic record or fundamental changes in geodynamic processes. An appraisal of the global geologic record from about 2.3 to 2.2 billion years ago demonstrates a Palaeoproterozoic tectono-magmatic lull. During this lull, global-scale continental magmatism (plume and arc magmatism) and orogenic activity decreased. There was also a lack of passive margin sedimentation and relative plate motions were subdued. A global compilation of mafic igneous rocks demonstrates that this episode of magmatic quiescence was terminated about 2.2 billion years ago by a flare-up of juvenile magmatism. This post-lull magmatic flare-up is distinct from earlier such events, in that the material extracted from the mantle during the flare-up yielded significant amounts of continental material that amalgamated to form Nuna — Earth’s first hemispheric supercontinent. We posit that the juvenile magmatic flare-up was caused by the release of significant thermal energy that had accumulated over some time. This flux of mantle-derived energy could have provided a mechanism for dramatic growth of continental crust, as well as the increase in relative plate motions required to complete the transition to modern plate tectonics and the supercontinent cycle. These events may also be linked to Palaeoproterozoic atmospheric oxygenation and equilibration of the carbon cycle

Dust outpaces bedrock in nutrient supply to montane forest ecosystems

Dust provides ecosystem-sustaining nutrients to landscapes underlain by intensively weathered soils. Here we show that dust may also be crucial in montane forest ecosystems, dominating nutrient budgets despite continuous replacement of depleted soils with fresh bedrock via erosion. Strontium and neodymium isotopes in modern dust show that Asian sources contribute 18–45% of dust deposition across our Sierra Nevada, California study sites. The remaining dust originates regionally from the nearby Central Valley. Measured dust fluxes are greater than or equal to modern erosional outputs from hillslopes to channels, and account for 10–20% of estimated millennial-average inputs of bedrock P. Our results demonstrate that exogenic dust can drive the evolution of nutrient budgets in montane ecosystems, with implications for predicting forest response to changes in climate and land use