Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56bright and CD56dim) exist in humans and ...have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much broader than originally appreciated as a result of variegated surface receptor, intracellular signaling molecule, and transcription factor expression; tissue-specific imprinting; and foreign antigen exposure. The recent discoveries of tissue-resident NK cell developmental intermediates, non-NK innate lymphoid cells, and the capacity for NK cells to adapt and differentiate into long-lived memory cells has added further complexity to this field. Here we review our current understanding of the breadth and generation of human NK cell diversity.
Recent advances in the field of human natural killer cell biology have revealed that there is a remarkably high amount of cellular diversity within different tissues. Freud et al. review these advances and provide insight into the generation of natural killer cell diversity and its roles in innate immunity.
Abstract
We present Atacama Large Millimeter/sub-millimeter Array (ALMA) Cycle 2 observations of the 1.3-mm dust continuum emission of the protoplanetary disc surrounding the T Tauri star Elias 24 ...with an angular resolution of ∼0.2 arcsec (∼28 au). The dust continuum emission map reveals a dark ring at a radial distance of 0.47 arcsec (∼65 au) from the central star, surrounded by a bright ring at 0.58 arcsec (∼81 au). In the outer disc, the radial intensity profile shows two inflection points at 0.71 and 0.87 arcsec (∼99 and 121 au, respectively). We perform global three-dimensional smoothed particle hydrodynamic gas/dust simulations of discs hosting a migrating and accreting planet. Combining the dust density maps of small and large grains with three-dimensional radiative transfer calculations, we produce synthetic ALMA observations of a variety of disc models in order to reproduce the gap- and ring-like features observed in Elias 24. We find that the dust emission across the disc is consistent with the presence of an embedded planet with a mass of ∼0.7 MJ at an orbital radius of ∼ 60 au. Our model suggests that the two inflection points in the radial intensity profile are due to the inward radial motion of large dust grains from the outer disc. The surface brightness map of our disc model provides a reasonable match to the gap- and ring-like structures observed in Elias 24, with an average discrepancy of ∼5 per cent of the observed fluxes around the gap region.
Interleukin 15 (IL-15) is one of the most important cytokines that regulate the biology of natural killer (NK) cells
. Here we identified a signaling pathway-involving the serine-threonine kinase AKT ...and the transcription factor XBP1s, which regulates unfolded protein response genes
-that was activated in response to IL-15 in human NK cells. IL-15 induced the phosphorylation of AKT, which led to the deubiquitination, increased stability and nuclear accumulation of XBP1s protein. XBP1s bound to and recruited the transcription factor T-BET to the gene encoding granzyme B, leading to increased transcription. XBP1s positively regulated the cytolytic activity of NK cells against leukemia cells and was also required for IL-15-mediated NK cell survival through an anti-apoptotic mechanism. Thus, the newly identified IL-15-AKT-XBP1s signaling pathway contributes to enhanced effector functions and survival of human NK cells.
Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past ...40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age ≥45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.
Context. For over a decade, the structure of the inner cavity in the transition disk of TW Hydrae has been a subject of debate. Modeling the disk with data obtained at different wavelengths has led ...to a variety of proposed disk structures. Rather than being inconsistent, the individual models might point to the different faces of physical processes going on in disks, such as dust growth and planet formation. Aims. Our aim is to investigate the structure of the transition disk again and to find to what extent we can reconcile apparent model differences. Methods. A large set of high-angular-resolution data was collected from near-infrared to centimeter wavelengths. We investigated the existing disk models and established a new self-consistent radiative-transfer model. A genetic fitting algorithm was used to automatize the parameter fitting, and uncertainties were investigated in a Bayesian framework. Results. Simple disk models with a vertical inner rim and a radially homogeneous dust composition from small to large grains cannot reproduce the combined data set. Two modifications are applied to this simple disk model: (1) the inner rim is smoothed by exponentially decreasing the surface density in the inner ~3 AU, and (2) the largest grains (>100 μm) are concentrated towards the inner disk region. Both properties can be linked to fundamental processes that determine the evolution of protoplanetary disks: the shaping by a possible companion and the different regimes of dust-grain growth, respectively. Conclusions. The full interferometric data set from near-infrared to centimeter wavelengths requires a revision of existing models for the TW Hya disk. We present a new model that incorporates the characteristic structures of previous models but deviates in two key aspects: it does not have a sharp edge at 4 AU, and the surface density of large grains differs from that of smaller grains. This is the first successful radiative-transfer-based model for a full set of interferometric data.
In automated surveillance, one is often interested in tracking road vehicles, measuring their shape in 3D world space, and determining vehicle classification. To address these tasks simultaneously, ...an effective approach is the constrained alignment of a prior model of 3D vehicle shape to images. Previous 3D vehicle models are either generic but overly simple or rigid and overly complex. Rigid models represent exactly one vehicle design, so a large collection is needed. A single generic model can deform to a wide variety of shapes, but those shapes have been far too primitive. This paper uses a generic 3D vehicle model that deforms to match a wide variety of passenger vehicles. It is adjustable in complexity between the two extremes. The model is aligned to images by predicting and matching image intensity edges. Novel algorithms are presented for fitting models to multiple still images and simultaneous tracking while estimating shape in video. Experiments compare the proposed model to simple generic models in accuracy and reliability of 3D shape recovery from images and tracking in video. Standard techniques for classification are also used to compare the models. The proposed model outperforms the existing simple models at each task.
We present 7-mm continuum observations of 14 low-mass pre-main-sequence stars in the Taurus-Auriga star-forming region obtained with the Very Large Array with ~1$.\!\!^{\prime\prime}$5 resolution and ...~0.3 mJy rms sensitivity. For 10 objects, the circumstellar emission has been spatially resolved. The large outer disk radii derived suggest that the emission at this wavelength is mostly optically thin. The millimetre spectral energy distributions are characterised by spectral indices $\alpha_{\rm mm}=$ 2.3 to 3.2. After accounting for contributions from free-free emission and corrections for optical depth, we determine dust opacity indices β in the range 0.5 to 1.6, which suggest that millimetre-sized dust aggregates are present in the circumstellar disks. Four of the sources with $\beta>1$ may be consistent with submicron-sized dust as found in the interstellar medium. Our findings indicate that dust grain growth to millimetre-sized particles is completed within less than 1 Myr for the majority of circumstellar disks.
ABSTRACT We describe the motivation, design, and implementation of the CORNISH survey, an arcsecond-resolution radio continuum survey of the inner galactic plane at 5 GHz using the Very Large Array ...(VLA). It is a blind survey coordinated with the northern Spitzer GLIMPSE I region covering 10° < l < 65° and |b| < 1° at similar resolution. We discuss in detail the strategy that we employed to control the shape of the synthesised beam across this survey, which covers a wide range of fairly low declinations. Two snapshots separated by 4h kept the beam elongation to less that 1.5 over 75% of the survey area and less than 2 over 98% of the survey. The prime scientific motivation is to provide an unbiased survey for ultra-compact H II regions to study this key phase in massive star formation. A sensitivity around 2 mJy will allow the automatic distinction between radio-loud and radio-quiet mid-IR sources found in the Spitzer surveys. This survey has many legacy applications beyond star formation, including evolved stars, active stars and binaries, and extragalactic sources. The CORNISH survey for compact ionized sources complements other Galactic plane surveys that target diffuse and nonthermal sources, as well as atomic and molecular phases to build up a complete picture of the interstellar medium in the Galaxy.
Treatment limitations exist for drug-resistant Acinetobacter baumannii central nervous system (CNS) infection. We conducted a retrospective study and systematic literature review to identify patients ...with drug-resistant A. baumannii CNS infection who received primary or adjunct intrathecal or intraventricular (IT/IVT) colistin. In a case series of seven Thai patients and 17 patients identified in the literature, clinical and microbiological cure rates with IT/IVT colistin therapy were 83% and 92%, respectively. Three patients (13%) developed chemical ventriculitis and one (4%) experienced treatment-associated seizures. Death was associated with delayed IT/IVT colistin therapy compared to survival (mean time from diagnosis to IT/IVT colistin, 7 vs. 2 days; p 0.01). The only independent predictor of mortality was the severity of illness (APACHE II score > 19, adjusted odds ratio 49.5; 95% CI 1.7–1428.6; p 0.02). This case series suggests that administration of primary or adjunctive IT/IVT colistin therapy was effective for drug-resistant A. baumannii CNS infection.
According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells ...develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originated from a common CD34−CD117+ ILC precursor pool, final steps of ILC2 development deviated independently and became mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlapped. Moreover, we identified a CD34−CD117+ ILC precursor population that expressed CD56 and gave rise to NK cells and ILC3s but not to ILC2s. These data support a model of human ILC development distinct from the mouse, whereby human NK cells and ILC3s share a common developmental pathway separate from ILC2s.
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•Human NK cells, ILC2s, and ILC3s develop from tonsil CD34−CD117+ ILC precursors•A CD56+ subset of CD34−CD117+ precursors generates NK cells and ILC3s but not ILC2s•Human ILC development is distinct from the established murine model
Human innate lymphoid cells (ILCs) develop from tissue-resident ILC precursors (ILCPs) in secondary lymphoid tissues. Here, Chen et al. describe a model of human ILC development in tonsils in which NK cells and group 3 ILCs derive from a CD56+ subset of ILCPs that cannot differentiate into group 2 ILCs.
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