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Macrophages are highly plastic innate immune cells that adopt an important diversity of phenotypes in response to environmental cues. Helminth infections induce strong type 2 cell-mediated immune responses, characterized among other things by production of high levels of interleukin- (IL-) 4 and IL-13. Alternative activation of macrophages by IL-4 in vitro was described as an opposite phenotype of classically activated macrophages, but the in vivo reality is much more complex. Their exact activation state as well as the role of these cells and associated molecules in type 2 immune responses remains to be fully understood. We can take advantage of a variety of helminth models available, each of which have their own feature including life cycle, site of infection, or pathological mechanisms influencing macrophage biology. Here, we reviewed the recent advances from the laboratory mouse about macrophage origin, polarization, activation, and effector functions during parasitic helminth infection.

Non-coding RNAs play a significant role in viral infection cycles, with recent attention focused on circular RNAs (circRNAs) originating from various viral families. Notably, these circRNAs have been associated with oncogenesis and alterations in viral fitness. However, identifying their expression has proven more challenging than initially anticipated due to unique viral characteristics. This challenge has the potential to impede progress in our understanding of viral circRNAs. Key hurdles in working with viral genomes include: (1) the presence of repetitive regions that can lead to misalignment of sequencing reads, and (2) unconventional splicing mechanisms that deviate from conserved eukaryotic patterns. To address these challenges, we developed vCircTrappist, a bioinformatic pipeline tailored to identify backsplicing events and pinpoint loci expressing circRNAs in RNA sequencing data. Applying this pipeline, we obtained novel insights from both new and existing datasets encompassing a range of animal and human pathogens belonging to Herpesviridae, Retroviridae, Adenoviridae, Flaviviridae and Orthomyxoviridae families. Subsequent RT-PCR and Sanger sequencings validated the accuracy of the developed bioinformatic tool for a selection of new candidate virus-derived circRNAs. These findings demonstrate that vCircTrappist is an open and unbiased approach for comprehensive identification of virus-derived circRNAs.

Gillet and colleagues find that infection with a gammaherpesvirus confers strong and lasting protection against airway allergy through the replacement of lung-resident alveolar macrophages with recruited regulatory monocytes of bone marrow origin. The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the T H 2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection.

Streamflow is often the only variable used to evaluate hydrological models. In a previous international comparison study, eight research groups followed an identical protocol to calibrate 12 hydrological models using observed streamflow of catchments within the Meuse basin. In the current study, we quantify the differences in five states and fluxes of these 12 process-based models with similar streamflow performance, in a systematic and comprehensive way. Next, we assess model behavior plausibility by ranking the models for a set of criteria using streamflow and remote-sensing data of evaporation, snow cover, soil moisture and total storage anomalies. We found substantial dissimilarities between models for annual interception and seasonal evaporation rates, the annual number of days with water stored as snow, the mean annual maximum snow storage and the size of the root-zone storage capacity. These differences in internal process representation imply that these models cannot all simultaneously be close to reality. Modeled annual evaporation rates are consistent with Global Land Evaporation Amsterdam Model (GLEAM) estimates. However, there is a large uncertainty in modeled and remote-sensing annual interception. Substantial differences are also found between Moderate Resolution Imaging Spectroradiometer (MODIS) and modeled number of days with snow storage. Models with relatively small root-zone storage capacities and without root water uptake reduction under dry conditions tend to have an empty root-zone storage for several days each summer, while this is not suggested by remote-sensing data of evaporation, soil moisture and vegetation indices. On the other hand, models with relatively large root-zone storage capacities tend to overestimate very dry total storage anomalies of the Gravity Recovery and Climate Experiment (GRACE). None of the models is systematically consistent with the information available from all different (remote-sensing) data sources. Yet we did not reject models given the uncertainties in these data sources and their changing relevance for the system under investigation.

The paper presents a consistent micro-scale flood risk analysis procedure, relying on detailed 2D inundation modelling as well as on high resolution topographic and land use database. The flow model is based on the shallow-water equations, solved by means of a finite volume scheme on multi-block structured grids. Using highly accurate laser altimetry, the simulations are performed with a typical grid spacing of 2 m, which is fine enough to represent the flow at the scale of individual buildings. Consequently, the outcomes of hydraulic modelling constitute suitable inputs for the subsequent exposure analysis, performed at a micro-scale using detailed land use maps and geographic database. Eventually, the procedure incorporates social flood impact analysis and evaluation of direct economic damage to residential buildings. Besides detailing the characteristics and performance of the hydraulic model, the paper describes the flow of data within the overall flood risk analysis procedure and demonstrates its applicability by means of a case study, for which two different flood protection measures were evaluated.

Understanding the strengths and limitations of the modeling capacity of surface flooding in urbanized floodplains is of utmost importance as such events are becoming increasingly frequent and extreme. In this study, we assess two computational models against laboratory observations of surface urban flooding in a reduced‐scale physical model of idealized urban districts. Four urban layouts were considered, involving each three inlets and three outlets as well as a combination of three‐ and four‐branch crossroads together with open spaces. The first model (2D) solves the shallow‐water equations while the second one (3D) solves the Reynolds‐averaged Navier‐Stokes equations. Both models accurately predict the flow depths in the inlet branches. For the discharge partition between the outlets, deviations between the computations and laboratory observations remain close to the experimental uncertainties (maximum 2.5 percent‐points). The velocity fields computed in 3D generally match the measured surface velocity fields. In urban layouts involving mostly a network of streets, the depth‐averaged velocity fields computed by the 2D model agree remarkably well with those of the 3D model, with differences not exceeding 10%, despite the presence of helicoidal flow (revealed by the 3D computations). In configurations with large open areas, the 3D model captures generally well the trajectory and velocity distribution of main surface flow jet and recirculations; but the 2D model does not perform as well as it does in relatively channelized flow regions. Visual inspection of the jet trajectories computed by the 2D model in large open areas reveals that they substantially deviate from the observations. Plain Language Summary Advancing our modeling capacity of urban flooding is of utmost importance for improving the design of risk reduction measures. During extreme urban flooding, complex flow patterns develop in urban environments, involving three‐dimensional flow structures. Though, urban floods are commonly simulated with two‐dimensional computational models. So far, no detailed comparison between flow fields predicted by two‐ and three‐dimensional computational models were conducted and assessed against reference data such as experimental observations for representative configurations of urban flooding. In this study, we assess two computational models against laboratory observations of urban flooding in a reduced‐scale physical model of an idealized district. Key Points Predictions of 2D and 3D computational models were compared against laboratory experiments representing urban flooding in a steady‐state Both models perform equally well to predict upstream flow depth, outlet discharge partition, and velocity field in street networks In urban layouts with large open spaces, only the 3D model accurately predicts the velocity field

Alcelaphine herpesvirus 1 (AlHV-1) is a γ-herpesvirus (γ-HV) belonging to the macavirus genus that persistently infects its natural host, the wildebeest, without inducing any clinical sign. However, cross-transmission to other ruminant species causes a deadly lymphoproliferative disease named malignant catarrhal fever (MCF). AlHV-1 ORF73 encodes the latency-associated nuclear antigen (LANA)-homolog protein (aLANA). Recently, aLANA has been shown to be essential for viral persistence in vivo and induction of MCF, suggesting that aLANA shares key properties of other γ-HV genome maintenance proteins. Here we have investigated the evasion of the immune response by aLANA. We found that a glycin/glutamate (GE)-rich repeat domain was sufficient to inhibit in cis the presentation of an epitope linked to aLANA. Although antigen presentation in absence of GE was dependent upon proteasomal degradation of aLANA, a lack of GE did not affect protein turnover. However, protein self-synthesis de novo was downregulated by aLANA GE, a mechanism directly associated with reduced antigen presentation in vitro. Importantly, codon-modification of aLANA GE resulted in increased antigen presentation in vitro and enhanced induction of antigen-specific CD8+ T cell responses in vivo, indicating that mRNA constraints in GE rather than peptidic sequence are responsible for cis-limitation of antigen presentation. Nonetheless, GE-mediated limitation of antigen presentation in cis of aLANA was dispensable during MCF as rabbits developed the disease after virus infection irrespective of the expression of full-length or GE-deficient aLANA. Altogether, we provide evidence that inhibition in cis of protein synthesis through GE is likely involved in long-term immune evasion of AlHV-1 latent persistence in the wildebeest natural host, but dispensable in MCF pathogenesis.

Hookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50  Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA + regulatory T cell (T regs ) frequencies in both settings, markers of T regs function, including inducible T-cell costimulatory (ICOS), tumor necrosis factor receptor 2 (TNFR2), and latency-associated peptide (LAP), as well as in vitro T regs suppressive capacity were higher in natural infections. Taken together, this study provides unique insights into the immunological trajectories following a first-in-life hookworm infection compared to natural infections. Hookworm infection remains a threat to public health where economic factors restrict treatment and lack of effective vaccination have limited successful therapeutic control which results in reinfection in endemic areas. Here the authors use a controlled human hookworm infection model and use high dimensional single cell profiling to show that plasmacytoid dendritic cells and regulatory T cells profiles that resemble those seen during natural infections in endemic areas.