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Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.

Land public transport is an important link within and between cities, and how to control the transmission of COVID-19 in land public transport is a critical issue in our daily lives. However, there are still many inconsistent opinions and views about the spread of SARS-CoV-2 in land public transport, which limits our ability to implement effective interventions. The purpose of this review is to overview the literature on transmission characteristics and routes of the epidemic in land public transport, as well as to investigate factors affecting its spread and provide feasible measures to mitigate the infection risk of passengers. We obtained 898 papers by searching the Web of Science, Pubmed, and WHO global COVID database by keywords, and finally selected 45 papers that can address the purpose of this review. Land public transport is a high outbreak area for COVID-19 due to characteristics like crowding, inadequate ventilation, long exposure time, and environmental closure. Different from surface touch transmission and drop spray transmission, aerosol inhalation transmission can occur not only in short distances but also in long distances. Insufficient ventilation is the most important factor influencing long-distance aerosol transmission. Other transmission factors (e.g., interpersonal distance, relative orientation, and ambient conditions) should be noticed as well, which have been summarized in this paper. To address various influencing factors, it is essential to suggest practical and efficient preventive measures. Among these, increased ventilation, particularly the fresh air (i.e., natural ventilation), has proven to effectively reduce indoor infection risk. Many preventive measures are also effective, such as enlarging social distance, avoiding face-to-face orientation, setting up physical partitions, disinfection, avoiding talking, and so on. As research on the epidemic has intensified, people have broken down many perceived barriers, but more comprehensive studies on monitoring systems and prevention measures in land public transport are still needed.

Nature-based Solutions (NbSs) play a pivotal role in mitigating the impact of microclimates on human well-being. The effectiveness of NbSs is contingent upon the synergy between natural capital, defined by the ecological structure and functions of the ecosystem, and human-derived capital, encompassing the economic investments required for implementation. This study introduces a decision-making framework designed to evaluate the impact of NbSs and advocate for optimal solutions for human health at the local scale, amalgamating ecological and economic assessments. Physiological Equivalent Temperature (PET) was chosen as a key urban parameter to assess the efficacy of NbSs in mitigating urban microclimates and enhancing human health. The PET analysis was conducted using ENVI-met 5.0.3 software across diverse urban scenarios in Gallipoli city, Italy. Integrated with a cost–benefit analysis of NbSs considering various investment scenarios, the study aimed to identify the most effective solution. Results indicated positive effects of NbSs in open spaces and around building blocks where the PET levels remained below 30 °C. Conversely, scenarios without NbSs exhibited PETs exceeding 40 °C, with peaks of 50 °C, posing potential risks to human health. Considering the social and economic benefits associated with PET mitigation, the cost–benefit analysis suggests that implementing NbSs using a mix of young and mature plants in the initial phase is advantageous compared to using only young plants. Thus, in establishing NbSs, it is crucial to consider not only the quantity of vegetation but also the strategic timing of implementation. In conclusion, our work offers an innovative framework that combines ecological and economic perspectives, providing valuable insights for decision-makers in urban planning and promoting the practical application of NbSs for enhanced human well-being.

Urban water bodies play an important role in regulating the thermal environment in densely populated cities. Typical central urban areas along both sides of the Pearl River in Guangzhou are selected as study sites and have been divided into 25 local zones with different spatial morphology. Mobile surveys are performed on typical summer and winter days. After temporal correction processing, the spatial distribution patterns of air temperature (Ta) and relative humidity (RH) at different times along both sides of the Pearl River are obtained. The daily Ta in the waterfront blocks ranged from 31.5 °C to 39.4 °C during summer, and from 17.50 °C to 27.50 °C during winter. Daily RH ranged from 41.3% to 67.3% during summer and 48.2%–76.4% during winter. This study explored the effects of urban spatial morphology and river wind on the local thermal environment of the waterfront blocks. The results showed that the river wind can have cooling and humidifying effects, especially on the windward side of these waterfront zones. The spatial heterogeneity and spatial autocorrelation characteristics of the block-scale waterfront areas are discovered to be clustered in both seasons. This study contributes to the design and optimization of thermally friendly waterfront blocks.

Numerical simulation is vital for evaluating urban ventilation. However, accurate urban-scale ventilation modeling requires extensive building surface simulation for computational demand. The distributed drag force approach simplifies the urban canopy by modeling buildings as a porous volume that accounts for momentum and turbulence. This method is a practical solution for simulating urban airflow. The drag force coefficient (Cd) is a crucial aerodynamic parameter in this approach. This study examines how Cd varies with urban design parameters such as plan area density (λp), average building height (H), frontal area density (λf), floor aspect ratio (AR), and sky view factor (SVF). Employing extensive numerical simulations conducted under neutral atmospheric conditions, we explore ranges of λp = 0.04–0.07 and λf = 0.1–1.2. The numerical model has been validated against existing wind tunnel data. The results show that Cd is insensitive to the model scale and background wind speed. We discover a nonlinear relationship between Cd and the parameters λp, λf, and SVF. For urban layouts with cubic-shaped buildings, Cd peaks at different λp within the range of 0.2~0.8. When λp and H are constant, Cd has a linear relationship with AR and λf. It is recommended to use λp, SVF, and AR as predictors for Cd across various urban configurations.

Objective To explore the role of leptin in the onset and development of obesity-associated hypertension. Subjects and Methods A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Leptin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. Results Serum leptin levels statistically significantly positively correlated with BMI and WC, and negatively with the HDLC (high-density lipoprotein cholesterol), even after adjustment for age and gender. There was no significant difference in the serum leptin levels between the normal healthy group (NH group) and the newly diagnosed untreated just-hypertension group (JH group). And the same is between the newly diagnosed untreated obesity-hypertension group (OH group) and the newly diagnosed untreated just-obesity group (JO group). Multiple linear regression analysis indicated BMI and gender as significant independent correlates of serum leptin. Conclusions These results show leptin may not be essential but play an additive effect in the development of obesity-associated hypertension. Leptin may only play an additive effect role in the intricate interwoven network of regulators contributing to the development of hypertension in obese patients.

Objective To explore the role of adiponectin-resistin (AR) index as a better indicator of obesity-related hypertension. Method(s) This study continued a case control study that had finished recruiting 153 subjects divided as four characteristic groups. Fasting serum resistin levels (FSR) and Fasting serum adiponectin levels (FSA) were tested by ELISA. And, other related anthropometric clinical and metabolic data were collected. Analyzation on correlations between research index and differences between groups were done by SPSS. AR index’s performance was also validated by the receiver operating characteristic (ROC) curves, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). Result(s) The AR index was defined as 1+ log10(R0)-log10(A0). AUC of the AR index was 0.660 and NRI and IDI indicated AR index outperformed FSA alone. AR index statistically significantly negatively correlated with SB and DB and positively with ALB and SCR. AR index was statistically significantly different between the NH group and OH group and more specific than FSR alone as a biomarker of obesity-related hypertension. Conclusion(s) The AR index was more strongly associated with increased risk of obesity-related hypertension than the solely index of FSR or FSA and was useful for early diagnosis of obesity-related hypertension.

A novel flame retardant hexa (4- (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10 -sulfide)-hydroxymethylphenoxy) cyclotriphosphazene (HAP-DOPS) with double functional groups was synthesized, and poly (lactic acid) (PLA) composites were prepared by melt extrusion. The flame retardancy and thermal degradation behavior of flame retardant PLA composites were studied by limiting oxygen index (LOI), vertical burning test (UL-94), cone calorimeter test (CCT), and thermogravimetric-infrared spectroscopy analysis (TG-IR). The experimental results showed that HAP-DOPS had a good flame-retardant effect on PLA. At flame retardant content of 5 wt%, the PLA/HAP-DOPS composite achieved a V-0 rating (UL-94, 3.2 mm) and a LOI value of 26.6%. The heat release rate (HRR) and total heat release (THR) of PLA composites were decreased by adding HAP-DOPS. The flame retardancy index (FRI) of PLA/HAP-DOPS-7.5 wt% was 1.0257, which showed good flame retardancy. The results of TG-IR showed that HAP-DOPS mainly had a gas-phase flame-retardant effect in PLA.

Objective: To explore the role of resistin in the onset and development of obesity-related hypertension. Methods: Resistin serum levels were tested by ELISA in 153 adult subjects among four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Following, correlations between research index and differences between groups were analyzed using SPSS. Results: Serum resistin levels statistically significantly negatively correlated with SB, DB and BMI, but statistically significantly positively correlated with serum creatinine (SCR) and serum albumin (ALB), even after adjustment for age and/or gender. The serum level of resistin in the normal healthy subject group (NH) was higher than in other groups. Conclusions: Resistin’s role in the onset of obesity-related hypertension may be more important than what has been previously assumed. More pathway substances in the early onset of obesity-related hypertension should be tested. Abbreviations: WC, waist circumference; GGT, Gamma-glutamyltransferase; ALB, Albumin; ALT, Alanine aminotransferase; LDL, Low density lipoprotein cholesterol; TG, Triglyceride; HDLC, High density lipoprotein cholesterol; FA Fructosamine; SCR, serum creatinine; IB, Indirect bilirubin; ALP, Alkaline phosphatase; CB, Conjugated bilirubin; UREA, Urea; Ua, Uric acid; FBG, fasting blood glucose; TC, Total cholesterol; TB, Total bilirubin; TP, Total protein; TC/HDLC, TC/HDLC ratio; SB, systolic blood pressure; DB, diastolic blood pressure

Urban green and blue infrastructure (GBI) is effective in urban heat mitigation. However, the diurnal variations in the thermal regulation of GBI on different types of urban pedestrian walkways in the subtropical humid climate zone are unclear. Based on traverse measurements in January 2022, this study investigates how outdoor air temperature (Ta) and wet-bulb temperature (Tw) at the pedestrian level are affected by various urban morphology and GBI characteristics in the central urbanized area of Guangzhou (China). Six building-related, three vegetation-related, and three water-related parameters were applied in the analyses. Results show that green infrastructure (GI) has the strongest cooling effect (Pearson’s coefficient r = −0.33~−0.54) on Ta on cloudy evenings and the weakest cooling effect (r = −0.22~−0.32) on clear evenings. Blue infrastructure (BI) exhibits the highest correlations with the cooling effect for Ta on clear afternoons (r = −0.35~−0.51) and weaker, but more consistent, correlations throughout cloudy days (r = −0.23~−0.43). Strong correlations between GI and Tw cooling are observed in the morning and evening on clear days (r = −0.13~−0.48), while BI exhibits the strongest correlation with Tw cooling on clear afternoons (r = −0.13~−0.37). In addition, both GI and BI show a greater cooling effect on both Ta and Tw in low-rise areas compared to high-rise areas. Compared to the individual GI or BI, the integrated GBI has a higher cooling intensity for both Ta and Tw in high-rise areas. However, the cooling potential of integrated GBI is slightly lower for both Ta and Tw during noon and afternoon in low-rise areas. The findings of this study give insights into urban GBI planning and design of specific urban microclimate regulation strategies.

The coronaviruses have inflicted health and societal crises in recent decades. Both SARS CoV-1 and 2 are suspected to spread through outdoor routes in high-density cities, infecting residents in apartments on separate floors or in different buildings in many superspreading events, often in the absence of close personal contact. The viability of such mode of transmission is disputed in the research literature, and there is little evidence on the dose–response relationship at the apartment level. This paper describes a study to examine the viability of outdoor airborne transmission between neighboring apartments in high density cities. A first-principles model, airborne transmission via outdoor route (ATOR), was developed to simulate airborne pathogen generation, natural decay, outdoor dispersion, apartment entry, and inhalation exposure of susceptible persons in neighboring apartments. The model was partially evaluated using a smoke tracer experiment in a mock-up high-density city site and cross-checking using the computational fluid dynamics (CFD) models. The ATOR model was used to retrospectively investigate the relationship between viral exposure and disease infection at an apartment level in two superspreading events in Hong Kong: the SARS outbreak in Amoy Gardens and the COVID-19 outbreak in Luk Chuen House. Logistic regression results suggested that the predicted viral exposure was positively correlated with the probability of disease infection at apartment level for both events. Infection risks associated with the outdoor route transmission of SARS can be reduced to

Mechanical ventilation consumes a huge amount of global energy. Natural ventilation is a crucial solution for reducing energy consumption and enhancing the capacity of atmospheric self-purification. This paper evaluates the impacts of indoor-outdoor temperature differences on building ventilation and indoor-outdoor air pollutant dispersion in urban areas. The Computational Fluid Dynamics (CFD) method is employed to simulate the flow fields in the street canyon and indoor environment. Ventilation conditions of single-side ventilation mode and cross-ventilation mode are investigated. Air change rate, normalized concentration of traffic-related air pollutant (CO), intake fraction and exposure concentration are calculated to for ventilation efficiency investigation and exposure assessment. The results show that cross ventilation increases the air change rate for residential buildings under isothermal conditions. With the indoor-outdoor temperature difference, heating could increase the air change rate of the single-side ventilation mode but restrain the capability of the cross-ventilation mode in part of the floors. Heavier polluted areas appear in the upstream areas of single-side ventilation modes, and the pollutant can diffuse to middle-upper floors in cross-ventilation modes. Cross ventilation mitigates the environmental health stress for the indoor environment when indoor-outdoor temperature difference exits and the personal intake fraction is decreased by about 66% compared to the single-side ventilation. Moreover, the existence of indoor-outdoor temperature differences can clearly decrease the risk of indoor personal exposure under both two natural ventilation modes. The study numerically investigates the building ventilation and pollutant dispersion in the urban community with natural ventilation. The method and the results are helpful references for optimizing the building ventilation plan and improving indoor air quality.

This is one of a limited number of studies that investigates multimedia exposure to metal(loid)s and the related human health risks caused by atmospheric deposition in China and Asia. The aggregate multimedia human exposure included the accidental ingestion and dermal adsorption of soil and surface water, as well as the intake of grains, fruits, vegetables, meats and eggs, milk and dairy products, and freshwater fish. The values and variabilities of atmospheric deposition and exposure factors were identified as two major uncertainty sources. The annual variations in wet and bulk deposition were propagated from the variabilities of particulate matter (PM) × precipitation and the linear regressed coefficients of flux~PM × precipitation, and the annual variation in dry deposition was propagated by subtracting the wet deposition from the bulk deposition. The variabilities in the exposure factors were updated based on the latest published regional data. Long-term atmospheric deposition was identified as a vital source of Cd contamination in surface soil and freshwater bodies and As accumulation in freshwater fish. The noncarcinogenic (NC) risk probabilities caused by Cd were the highest, followed by As. The overall uncertainties related to the NC risk probabilities were much lower for both adults and 6- to 17-year-old children/adolescents, while those related to the carcinogenic risk (CR) probabilities were much lower for 2- to 5-year-old children and 6- to 17-year-old children/adolescents. Our results could help infer the cobenefits due to the current regional air pollution control policy. Keywords: Atmospheric deposition, Metal(loid)s, Environmental accumulation, Multimedia exposure, Health risk assessment

Background: CD38 is involved in the adenosine pathway, which represents one of the immunosuppressive mechanisms in cancer. CD38 is broadly expressed across immune cell subsets, including human macrophages differentiated in vitro from monocytes, but expression by tissue-resident macrophages remains to be demonstrated.Methods: Tissue samples were obtained from 66 patients with hepatocellular carcinoma (HCC) from Singapore and analyzed using immunohistochemistry. Tumor-infiltrating leukocytes (TILs) were further examined using DEPArray™, and the phenotype of freshly isolated TILs was determined using flow cytometry.Results: CD38 was frequently co-expressed with the macrophage-specific marker CD68. CD38+CD68+ macrophage density was associated with improved prognosis after surgery, while total CD68+ macrophage density was associated with poor prognosis. DEPArray™ analysis revealed the presence of large (>10 μm), irregularly shaped CD45+CD14+ cells that resembled macrophages, with concurrent CD38+ expression. Flow cytometry also revealed that majority of CD14+HLA-DR+ cells expressed CD38.Conclusion: CD38 expression was clearly demonstrated on human macrophages in an in vivo setting. The positive association identified between CD38+ macrophage density and prognosis may have implications for routine diagnostic work.

The Atmosphere Special Issue “Recent Advances in Urban Ventilation Assessment and FlowModelling” collects twenty-one original papers and one review paper published in 2017[...]

Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV) serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE) phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN) receptors-deficient mice (AG129) born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5-week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naïve mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFα therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of vaccine and therapeutic candidates.

Providing efficient ventilation in road tunnels is essential to prevent severe air pollution exposure for both drivers and pedestrians in such enclosed spaces with heavy vehicle emissions. Longitudinal ventilation methods like commercial jet fans have been widely applied and confirmed to be effective for introducing external fresh air into road tunnels that are shorter than 3 km. However, operating tunnel jet fans is energy consuming. Therefore, for small-scale (~100 m–1 km) road tunnels, mechanical ventilation methods might be highly energetically expensive and unaffordable. Many studies have found that the use of wind catchers could improve buildings’ natural ventilation, but their effect on improving natural ventilation in small-scale road tunnels has, hitherto, rarely been studied. This paper, therefore, aims to quantify the influence of style and arrangement of one-sided flat-roof wind catchers on ventilation performance in a road tunnel. The concept of intake fraction (IF) is applied for ventilation and pollutant exposure assessment in the overall tunnel and for pedestrian regions. Computational fluid dynamics (CFD) methodology with a standard k-epsilon turbulence model is used to perform a three-dimensional (3D) turbulent flow simulation, and CFD results have been validated by wind-tunnel experiments for building cross ventilation. Results show that the introduction of wind catchers would significantly enhance wind speed at pedestrian level, but a negative velocity reduction effect and a near-catcher recirculation zone can also be found. A special downstream vortex extending along the downstream tunnel is found, helping remove the accumulated pollutants away from the low-level pedestrian sides. Both wind catcher style and arrangement would significantly influence the ventilation performance in the tunnel. Compared to long-catcher designs, short-catchers would be more effective for providing fresh air to pedestrian sides due to a weaker upstream velocity reduction effect and smaller near-catcher recirculation zone. In long-catcher cases, IF increases to 1.13 ppm when the wind catcher is positioned 240 m away from the tunnel entrance, which is almost twice that in short-catcher cases. For the effects of catcher arrangements, single, short-catcher, span-wise, shifting would not help dilute pollutants effectively. Generally, a design involving a double short-catcher in a parallel arrangement is the most recommended, with the smallest IF, i.e., 61% of that in the tunnel without wind catchers (0.36 ppm).

Previous researchers calculated air change rate per hour (ACH) in the urban canopy layers (UCL) by integrating the normal component of air mean velocity (convection) and fluctuation velocity (turbulent diffusions) across UCL boundaries. However they are usually greater than the actual ACH induced by flow rates flushing UCL and never returning again. As a novelty, this paper aims to verify the exponential concentration decay history occurring in UCL models and applies the concentration decay method to assess the actual UCL ACH and predict the urban age of air at various points. Computational fluid dynamic (CFD) simulations with the standard k-ε models are successfully validated by wind tunnel data. The typical street-scale UCL models are studied under neutral atmospheric conditions. Larger urban size attains smaller ACH. For square overall urban form (Lx = Ly = 390 m), the parallel wind (θ = 0°) attains greater ACH than non-parallel wind (θ = 15°, 30°, 45°), but it experiences smaller ACH than the rectangular urban form (Lx = 570 m, Ly = 270 m) under most wind directions (θ = 30° to 90°). Open space increases ACH more effectively under oblique wind (θ = 15°, 30°, 45°) than parallel wind. Although further investigations are still required, this paper provides an effective approach to quantify the actual ACH in urban-like geometries.

Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved.

Polysaccharide (PS) capsules are important virulence determinants for many bacterial pathogens. Bordetella pertussis, the agent of whooping cough, produces a surface associated microcapsule but its role in pertussis pathogenesis remained unknown. Here we showed that the B. pertussis capsule locus is expressed in vivo in murine lungs and that absence of the membrane-associated protein KpsT, involved in the transport of the PS polymers across the envelope, but not the surface-exposed PS capsule itself, affects drastically B. pertussis colonization efficacy in mice. Microarray analysis revealed that absence of KpsT in B. pertussis resulted in global down-regulation of gene expression including key virulence genes regulated by BvgA/S, the master two-component system. Using a BvgS phase-locked mutant, we demonstrated a functional link between KpsT and BvgA/S-mediated signal transduction. Whereas pull-down assays do not support physical interaction between BvgS sensor and any of the capsule locus encoded proteins, absence of KpsT impaired BvgS oligomerization, necessary for BvgS function. Furthermore, complementation studies indicated that instead of KpsT alone, the entire PS capsule transport machinery spanning the cell envelope likely plays a role in BvgS-mediated signal transduction. Our work thus provides the first experimental evidence of a role for a virulence-repressed gene in pertussis pathogenesis.