Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing

The use of pneumococcal capsular polysaccharide (PPS)-based vaccines has resulted in a substantial reduction in invasive pneumococcal disease. However, much remains to be learned about vaccine-mediated immunity, as seven-valent PPS-protein conjugate vaccine use in children has been associated with nonvaccine serotype replacement and 23-valent vaccine use in adults has not prevented pneumococcal pneumonia. In this report, we demonstrate that certain PPS-specific monoclonal antibodies (MAbs) enhance the transformation frequency of two different Streptococcus pneumoniae serotypes. This phenomenon was mediated by PPS-specific MAbs that agglutinate but do not promote opsonic effector cell killing of the homologous serotype in vitro. Compared to the autoinducer, competence-stimulating peptide (CSP) alone, transcriptional profiling of pneumococcal gene expression after incubation with CSP and one such MAb to the PPS of serotype 3 revealed changes in the expression of competence (com)-related and bacteriocin-like peptide (blp) genes involved in pneumococcal quorum sensing. This MAb was also found to induce a nearly 2-fold increase in CSP2-mediated bacterial killing or fratricide. These observations reveal a novel, direct effect of PPS-binding MAbs on pneumococcal biology that has important implications for antibody immunity to pneumococcus in the pneumococcal vaccine era. Taken together, our data suggest heretofore unsuspected mechanisms by which PPS-specific antibodies could affect genetic exchange and bacterial viability in the absence of host cells

Current exposure to environmental pollutants in the general adult population of Kinshasa, Democratic Republic of Congo (DRC): A cross-sectional study

peer reviewedBackground : Environmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low. Objective : To measure contamination by arsenic, lead, 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population. Methods : In the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4′-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC). Results : The PCBs 180, -153 and −138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4′-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes. Conclusions : Our results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure

Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo▿

Acquired antibody immunity to Streptococcus pneumoniae (pneumococcus) has been linked to serotype (ST)-specific opsonic antibodies to the relevant pneumococcal capsular polysaccharide (PPS) that mediate protection by enhancing the bactericidal effect of host phagocytes. Despite the well-recognized role of opsonic IgG in host defense against pneumococcus, PPS-specific monoclonal antibodies (MAbs) that mediate protection against lethal challenge with ST3 pneumococcus in mice but do not promote phagocytic killing in vitro (nonopsonic antibodies) have been described. In this study, we sought to determine the biological activity of one such MAb, A7 (a human PPS3-specific IgM), and the mechanism by which it mediates protection. In vitro studies demonstrated that coincubation of A7 with ST3 in the absence of phagocytes or a complement source resulted in a reduction in CFU on blood agar plates that was largely reversible by sonication. A chromogenic cellular proliferation assay demonstrated that A7 did not affect replication of ST3 in liquid culture. The ability of A7 to induce aggregation of ST3 was confirmed by fluorescence microscopy and flow cytometry: A7 induced aggregation of ST3, and in the presence of a complement source, A7 promoted deposition of complement component 3 (C3) on aggregated bacteria in a dose-dependent fashion. Similarly, administration of preincubated mixtures of A7 and ST3 intraperitoneally to mice protected them from the lethality of ST3 in a dose-dependent fashion. These findings suggest that A7-mediated aggregation enhances resistance to ST3, most likely by enhancing C3 deposition on the ST3 capsule, thereby promoting host antipneumococcal activity in vivo

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified