Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis

Innate immunity is the most broadly effective host defense, being essential to clear the majority of microbial infections. Scavenger Receptors comprise a family of sensors expressed in a multitude of host cells, whose dual role during microbial pathogenesis gained importance over recent years. SRs regulate the recruitment of immune cells and control both host inflammatory response and bacterial load. In turn, pathogens have evolved different strategies to overcome immune response, avoid recognition by SRs and exploit them to favor infection. Here, we discuss the most relevant findings regarding the interplay between SRs and pathogens, discussing how these multifunctional proteins recognize a panoply of ligands and act as bacterial phagocytic receptors.This work received funding from Norte-01–0145-FEDER-000012– Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL Partnership Agreement, through the European Regional Development Fund (FEDER). R.P received an FCT Doctoral Fellowship [SFRH/BD/89542/2012] through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT)

Argo salinity: bias and uncertainty evaluation

Argo salinity is a key set of in situ ocean measurements for many scientific applications. However, use of the raw, unadjusted salinity data should be done with caution as they may contain bias from various instrument problems, most significant being from sensor calibration drift in the conductivity cells. For example, inclusion of biased but unadjusted Argo salinity has been shown to lead to spurious results in the global sea level estimates. Argo delayed-mode salinity data are data that have been evaluated and, if needed, adjusted for sensor drift. These delayed-mode data represent an improvement over the raw data because of the reduced bias, the detailed quality control flags, and the provision of uncertainty estimates. Such improvement may help researchers in scientific applications that are sensitive to salinity errors. Both the raw data and the delayed-mode data can be accessed via https://doi.org/10.17882/42182 (Argo, 2022). In this paper, we first describe the Argo delayed-mode process. The bias in the raw salinity data is then analyzed by using the adjustments that have been applied in delayed mode. There was an increase in salty bias in the raw Argo data beginning around 2015 and peaking during 2017–2018. This salty bias is expected to decrease in the coming years as the underlying manufacturer problem has likely been resolved. The best ways to use Argo data to ensure that the instrument bias is filtered out are then described. Finally, a validation of the Argo delayed-mode salinity dataset is carried out to quantify residual errors and regional variations in uncertainty. These results reinforce the need for continual re-evaluation of this global dataset.</p

Stathmin recruits tubulin to Listeria monocytogenes-induced actin comets and promotes bacterial dissemination

The tubulin cytoskeleton is one of the main components of the cytoarchitecture and is involved in several cellular functions. Here, we examine the interplay between Listeria monocytogenes (Lm) and the tubulin cytoskeleton upon cellular infection. We show that non-polymeric tubulin is present throughout Lm actin comet tails and, to a less extent, in actin clouds. Moreover, we demonstrate that stathmin, a regulator of microtubule dynamics, is also found in these Lm-associated actin structures and is required for tubulin recruitment. Depletion of host stathmin results in longer comets containing less F-actin, which may be correlated with higher levels of inactive cofilin in the comet, thus suggesting a defect on local F-actin dynamics. In addition, intracellular bacterial speed is significantly reduced in stathmin-depleted cells, revealing the importance of stathmin/tubulin in intracellular Lm motility. In agreement, the area of infection foci and the total bacterial loads are also significantly reduced in stathmin-depleted cells. Collectively, our results demonstrate that stathmin promotes efficient cellular infection, possibly through tubulin recruitment and control of actin dynamics at Lm-polymerized actin structures.This work received funding from Norte-01-0145-FEDER-000012—Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). ACC and FC were supported by a Fundação para a Ciência e Tecnologia (FCT) Post-doctoral Fellowship (SFRH/BPD/88769/2012) and Ph.D. fellowship (SFRH/BD/61825/2009), respectively, through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT). We thank ALM unit from IBMC/i3S for technical support, B. Fonseca (FFUP) for the BeWo cell line and H. Maiato, C. Sunkel and J. B. Relvas laboratories (IBMC/i3S) for sharing reagents. We are also thankful to J. Ferreira and A. Pereira for fruitful discussions

Eddy-wave duality in a rotating flow

A series of experiments with rotating, electromagnetically forced, turbulent flows were carried out at the Sapienza University of Rome to investigate the eddy-wave duality in flows with a β-effect and the electromagnetic force acting in the westward direction. When the β-effect is significant, i.e., as in planetary atmospheric and oceanic circulations, nonlinear eddy/wave interactions facilitate flow self-organization into zonal patterns in which Rossby waves and westward propagating cyclonic and anticyclonic eddies coexist. Upon time averaging, eddies disappear and the flow pattern transforms into a system of alternating zonal jets. What is the relationship between eddies, jets, and Rossby waves? To address this issue, we designed a laboratory experiment in which a westward zonal flow is produced by applying an electromagnetic small-scale forcing to a thin layer of a rotating fluid. In order to investigate different levels of flow zonality and a wider range of zonal modes, we varied the forcing intensity and the area of the forced sector. The zonal flow evolves as a system of westward propagating, large scale, cyclonic, and anticyclonic eddies. The propagation speed of the traveling structures was calculated from the Hovmöller diagrams of both the streamfunction and the centroids of clusters of different types (cyclonic and anticyclonic eddy cores and saddle point neighborhoods) obtained via an Okubo-Weiss analysis. The results were compared with the theoretical phase speed of a Rossby wave. The correspondence between these two characteristics at the radius of maximum shear corresponding to the epicenter of the barotropic instability is quite good, particularly after including the radial variation of the zonal velocity in the β-term. It is concluded that the Rossby waves and eddies are inseparable as the former maintain the instability that sustains the latter. This symbiosis visually resembles the Rossby soliton

Argo salinity: bias and uncertainty evaluation

Argo salinity is a key set of in situ ocean measurements for many scientific applications. However, use of the raw, unadjusted salinity data should be done with caution as they may contain bias from various instrument problems, most significant being from sensor calibration drift in the conductivity cells. For example, inclusion of biased but unadjusted Argo salinity has been shown to lead to spurious results in the global sea level estimates. Argo delayed-mode salinity data are data that have been evaluated and, if needed, adjusted for sensor drift. These delayed-mode data represent an improvement over the raw data because of the reduced bias, the detailed quality control flags, and the provision of uncertainty estimates. Such improvement may help researchers in scientific applications that are sensitive to salinity errors. Both the raw data and the delayed-mode data can be accessed via https://doi.org/10.17882/42182 (Argo, 2022). In this paper, we first describe the Argo delayed-mode process. The bias in the raw salinity data is then analyzed by using the adjustments that have been applied in delayed mode. There was an increase in salty bias in the raw Argo data beginning around 2015 and peaking during 2017–2018. This salty bias is expected to decrease in the coming years as the underlying manufacturer problem has likely been resolved. The best ways to use Argo data to ensure that the instrument bias is filtered out are then described. Finally, a validation of the Argo delayed-mode salinity dataset is carried out to quantify residual errors and regional variations in uncertainty. These results reinforce the need for continual re-evaluation of this global dataset.</p

Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation, and cancer; however, its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane. We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.This work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project UIDB/04293/2020. R.P. and J.P. were supported by doctoral fellowships from FCT (SFRH/BD/89542/2012 and SFRH/BD/86871/2012). S.S. was supported by the FCT in the framework of the CEEC-Institutional 2017 program. The authors acknowledge the support of i3S Scientific Platforms: Advanced Light Microscopy, member of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01-0145-FEDER-022122), and Translational Cytometry Unit (Tracy);Fundação para a Ciência e a Tecnologia [UIDB/04293/2020]

Three examples where the specific surface area of snow increased over time

Snow on the ground impacts climate through its high albedo and affects atmospheric composition through its ability to adsorb chemical compounds. The quantification of these effects requires the knowledge of the specific surface area (SSA) of snow and its rate of change. All relevant studies indicate that snow SSA decreases over time. Here, we report for the first time three cases where the SSA of snow increased over time. These are (1) the transformation of a melt-freeze crust into depth hoar, producing an increase in SSA from 3.4 to 8.8m2 kg−1. (2) The mobilization of surface snow by wind, which reduced the size of snow crystals by sublimation and fragmented them. This formed a surface snow layer with a SSA of 61m2 kg−1 from layers whose SSAs were originally 42 and 50m2 kg−1. (3) The sieving of blowing snow by a snow layer, which allowed the smallest crystals to penetrate into open spaces in the snow, leading to an SSA increase from 32 to 61m2 kg−1. We discuss that other mechanisms for SSA increase are possible. Overall, SSA increases are probably not rare. They lead to enhanced uptake of chemical compounds and to increases in snow albedo, and their inclusion in relevant chemical and climate models deserves consideration

Perfringolysin O-induced plasma membrane pores trigger actomyosin remodeling and endoplasmic reticulum redistribution

Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other toxins to determine the outcome of the infection. However, its individual contribution to the disease is poorly understood. Here, we intoxicated human epithelial and endothelial cells with purified PFO to evaluate the host cytoskeletal responses to PFO-induced damage. We found that, at sub-lytic concentrations, PFO induces a profound reorganization of the actomyosin cytoskeleton culminating into the assembly of well-defined cortical actomyosin structures at sites of plasma membrane (PM) remodeling. The assembly of such structures occurs concomitantly with the loss of the PM integrity and requires pore-formation, calcium influx, and myosin II activity. The recovery from the PM damage occurs simultaneously with the disassembly of cortical structures. PFO also targets the endoplasmic reticulum (ER) by inducing its disruption and vacuolation. ER-enriched vacuoles were detected at the cell cortex within the PFO-induced actomyosin structures. These cellular events suggest the targeting of the endothelium integrity at early stages of C. perfringens infection, in which secreted PFO is at sub-lytic concentrations.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-030863 (PTDC/BIA-CEL/30863/2017) and Norte-01-0145-FEDER-000012—Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Publication Fees were supported by ICBAS, University of Porto. CB and FSM were supported by FCT fellowships (SFRH/BD/112217/2015, SFRH/BPD/94458/2013, respectively). CB was a Fulbright and FLAD fellow. SS received support from FCT Investigator program (COMPETE, POPH, and FCT)

Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.This work received funding from Norte-01-0145-FEDER-000012 - Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Publication Fees were supported by ICBAS, University of Porto. RC received an FCT Doctoral Fellowship (SFRH/BD/90607/2012) and IP-C a FCT Post-Doctoral Fellowship (SFRH/BPD/107901/2015) through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT). We thank IBMC facilities for technical assistance

Old war, new battle, new fighters!

This work was supported by the Fundo Europeu de Desenvolvimento Regional – Programa Operacional Factores de Competitividade (FEDER-COMPETE) and Fundação para a Ciência e a Tecnologia (FCT) (PTDC/BIA-BCM/111215/2009FCOMP-01-0124- FEDER-014178, PTDC/SAU-MIC/111581/2009 FCOMP-01-0124-FEDER-0158449, and InfectERA PROANTILIS/0001/2013 to D. C.), the European Molecular Biology Organization (EMBO) (to F. S. M.), and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (to S. S.)