Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the ...level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously.
Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina ...propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64− DCs and contaminating CSF-1R-dependent CD24−CD64+ macrophages. Functionally, loss of CD24+CD11b+ DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24+CD11b+ DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.
•Mucosal CD11b+ DCs consist of CD24+CD64− DCs and CD24−CD64+ macrophages•Mucosal CD24+CD11b+ DCs are IRF4-dependent•IRF4-dependent CD24+CD11b+ DCs secrete IL-23α and control mucosal IL-17 responses•Human CD1c+CD11b+ DCs are functional homologs of murine CD24+CD11b+ DCs
The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has ...been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9− pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9+ pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9− pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9− pDC-like precursors differentiate into CCR9+ pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9− pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9− pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.
Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, ...leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after
stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.
Tritium and helium isotope data provide key information on ocean
circulation, ventilation, and mixing, as well as the rates of biogeochemical
processes and deep-ocean hydrothermal processes. We ...present here global
oceanic datasets of tritium and helium isotope measurements made by numerous
researchers and laboratories over a period exceeding 60 years. The dataset's
DOI is https://doi.org/10.25921/c1sn-9631, and the data are available at
https://www.nodc.noaa.gov/ocads/data/0176626.xml (last access: 15 March
2019) or alternately
http://odv.awi.de/data/ocean/jenkins-tritium-helium-data-compilation/
(last access: 13 March 2019) and includes approximately 60 000 valid tritium
measurements, 63 000 valid helium isotope determinations, 57 000 dissolved
helium concentrations, and 34 000 dissolved neon concentrations. Some
quality control has been applied in that questionable data have been flagged
and clearly compromised data excluded entirely. Appropriate metadata have
been included, including geographic location, date, and sample depth. When
available, we include water temperature, salinity, and dissolved oxygen. Data
quality flags and data originator information (including methodology) are
also included. This paper provides an introduction to the dataset along with
some discussion of its broader qualities and graphics.
Plasmacytoid dendritic cells (PDCs) are capable of presenting Ags to T cells in a tolerogenic or immunogenic manner depending on the formulation of the Ag and the mode of stimulation. It has not been ...investigated whether effective adaptive immune responses useful for vaccination can be induced by Ab-mediated Ag targeting to PDCs in vivo. In this study, we show that Ag delivered to murine PDCs via bone marrow stromal cell Ag 2 (BST2)/CD317 in combination with TLR agonists as adjuvants is specifically presented by PDCs in vivo and elicits strong cellular and humoral immune responses. These include IFN-γ production by CD4(+) T cells and high Ab titers with a broad range of IgG isotypes. In addition, BST2-mediated Ag delivery in the presence of polyinosinic-polycytidylic acid as adjuvant induces cytotoxic T lymphocytes that are functional in vivo. A single immunization with Ag-fused anti-BST2 Ab together with polyinosinic-polycytidylic acid as adjuvant is sufficient to trigger protective immunity against subsequent viral infection and tumor growth. We conclude that despite the potential tolerogenic properties of PDCs, Ag targeting to PDCs in combination with TLR agonists as adjuvants is an effective vaccination strategy.
Trafficking of lung dendritic cells (DCs) to the draining lymph node (dLN) is a crucial step for the initiation of T cell responses upon pathogen challenge. However, little is known about the factors ...that regulate lung DC migration to the dLN. In this study, using a model of influenza infection, we demonstrate that complement component C3 is critically required for efficient emigration of DCs from the lung to the dLN. C3 deficiency affect lung DC-mediated viral antigen transport to the dLN, resulting in severely compromised priming of virus-specific T cell responses. Consequently, C3-deficient mice lack effector T cell response in the lungs that affected viral clearance and survival. We further show that direct signaling by C3a and C5a through C3aR and C5aR respectively expressed on lung DCs is required for their efficient trafficking. However, among lung DCs, only CD103(+) DCs make a significant contribution to lung C5a levels and exclusively produce high levels of C3 and C5 during influenza infection. Collectively, our findings show that complement has a profound impact on immune regulation by controlling tissue DC trafficking and highlights a potential utility for complement as an adjuvant in novel vaccine strategies.
For the determination of the elemental composition of particulate organic material (POM) and its impact on the marine carbon cycle, we assembled C:N data for POM from many different sources into a ...single data collection for joint evaluation. The data set contains 10,200 C:N values, encompassing all major oceans and trophic levels, showing that C:N ratios are highly variable with values below the traditional Redfield ratio (C:N = 6.6) to values greatly exceeding it. On a global mean, C:N ratios of marine sinking particles from the surface water amount to 7.1 ± 0.1, and there is a systematic increase of C:N ratios with depth of 0.2 ± 0.1 units per 1000 m. The discrepancy with results from analyses of dissolved nutrient fields, yielding constant C:N ratios close to the Redfield value, can be explained by the implicit depth averaging caused by depth variations of the surfaces under consideration. Additionally, due to preferential remineralization of nitrogen compared to carbon, the C:N ratio of the dissolving component, which is seen on dissolved nutrient fields, is smaller than the C:N ratio of the remaining particles. For carbon flux estimations, elevated and depth dependent C:N ratios should be implemented in biogeochemical models to correctly represent relative strengths of downward carbon and nitrogen fluxes.
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