Abstract 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.
Helminth infections induce strong type 2 and regulatory responses, but the degree of heterogeneity of such cells is not well characterized. Using mass cytometry, we profiled these cells in Europeans ...and Indonesians not exposed to helminths and in Indonesians residing in rural areas infected with soil-transmitted helminths. To assign immune alteration to helminth infection, the profiling was performed before and 1 year after deworming. Very distinct signatures were found in Europeans and Indonesians, showing expanded frequencies of T helper 2 cells, particularly CD161
cells and ILC2s in helminth-infected Indonesians, which was confirmed functionally through analysis of cytokine-producing cells. Besides ILC2s and CD4
T cells, CD8
T cells and γδ T cells in Indonesians produced type 2 cytokines. Regulatory T cells were also expanded in Indonesians, but only those expressing CTLA-4, and some coexpressed CD38, HLA-DR, ICOS, or CD161. CD11c
B cells were found to be the main IL-10 producers among B cells in Indonesians, a subset that was almost absent in Europeans. A number of the distinct immune profiles were driven by helminths as the profiles reverted after clearance of helminth infections. Moreover, Indonesians with no helminth infections residing in an urban area showed immune profiles that resembled Europeans rather than rural Indonesians, which excludes a major role for ethnicity. Detailed insight into the human type 2 and regulatory networks could provide opportunities to target these cells for more precise interventions.
Abstract De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another ...mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues.
Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune ...signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161
CD4
T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4
T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.
In this paper, we investigate regional differences in the gender pay gap both theoretically and empirically. Within a spatial model of monopsonistic competition, we show that more densely populated ...labour markets are more competitive and constrain employers’ ability to discriminate against women. Utilizing a large administrative data set for western Germany and a flexible semi‐parametric propensity score matching approach, we find that the unexplained gender pay gap for young workers is substantially lower in large metropolitan than in rural areas. This regional gap in the gap of roughly 10 percentage points remained surprisingly constant over the entire observation period of 30 years.
Purpose - In 1997 minimum wages were introduced in the West and East German construction sector. The purpose of this paper is to analyze their impact on wage growth and employment retention ...probability of affected workers.Design methodology approach - Following a difference-in-differences approach the paper proposes a method to identify the effects of this quasi-experiment despite the lack of information on working hours in the large panel microdata. The method determines the size of the treatment and control group by the maximum likelihood criterion.Findings - All results show positive wage growth effects of the minimum wage regulation in both parts of the country. When it comes to employment effects, the results clearly differ between the two parts of the country. The employment effects are negative for East Germany and positive for West Germany, although the latter are not always statistically significant.Research limitations implications - Although there is a limit to the simple transferability of the results for the construction sector to other industries, the study provides some useful insights for this country concerning reactions to the minimum wage. This is the first paper analyzing the effect of minimum wages in Germany using microeconometric methods.Practical implications - As the minimum wage in the East German construction sector was much higher in relation to the median wage than in West Germany, a tentative conclusion of the different employment results might be that the trade-off between increasing wages for low-paid workers and the danger of job losses does not exist in this case if minimum wages are moderate.Originality value - This paper provides valuable information on the impact of wage growth and employment retention probability in Germany.
This contribution focuses on the relation between wage inequality, participation behavior and employment and the analysis in the project 'Flexibility of the wage distribution, inequality and ...employment'. In this project we investigate whether the popular idea of an encrusted German labor market with institutional regulations, minimum wages, high reservation wages, union power or insider behavior is consistent with the actual conditions. At first we critically assess the hypothesis that wage compression in Germany leads to employment losses. It can be shown theoretically that higher wage dispersion lower labor market participation as a negative side-effect. Empirical analyses support this result. A higher regional wage level as well as low unemployment -- as an indicator for the stability of jobs -- come along with high participation. A rise in wage dispersion in the lower part of the wage distribution is connected with decreasing employment participation, in the upper part with rising employment participation. As a further result it is shown that interdependencies between regions strongly matter. Additionally we highlight stylized facts about the development of wage inequality. We compare the US and Germany -- countries with high and low wage flexibility respectively -- based on harmonized micro data. We analyze the hypothesis that rigidities due to institutional influences imply a deformation of the wage distribution in the left tail. Such a characteristic wage compression would have to appear particularly for groups of low wage workers in countries like Germany. The comparison with the US labor market suggests the assumption that the deformation of the German wage structure with negative impacts on employment is a distorted picture. A further topic addresses the consequences of setting bounds to the extending inequality in the lower part of the wage distribution by introducing a wage floor. We focus on the effects of a minimum wage on wage inequality and employment. This minimum wage was introduced in 1997 in the German construction sector related to the German Workers Posting Law. We find positive wage effects of the minimum wage regulation in Eastern as well as in Western Germany, albeit the wage reaction in Eastern Germany was considerably larger. When it comes to employment effects, negative effects arise for Eastern Germany and positive for West Germany, although the latter are not always statistically significant. This result shows that a binding minimum wage does not necessarily imply negative employment effects. Finally, this contribution deals with a specific aspect of the wage inequality, the gender pay gap. The focus here is on the influence of the regional context. Having controlled for differences in individual characteristics, education and work places between men and women we show that the gender-specific wage differential is considerably higher in rural than in metropolitan areas. This differential has decreased notably in the last three decades in both regional types. The pay gap between young women and men in rural areas, in an environment with low firm density, is almost constantly ten percentage points higher during the whole observational period than in metropolitan settings. This result is consistent with a theoretical model that additionally takes into account market power of firms.
"This contribution focuses on the relation between wage inequality, participation behavior and employment and the analysis in the project 'Flexibility of the wage distribution, inequality and ...employment'. In this project we investigate whether the popular idea of an encrusted German labor market with institutional regulations, minimum wages, high reservation wages, union power or insider behavior is consistent with the actual conditions. At first we critically assess the hypothesis that wage compression in Germany leads to employment losses. It can be shown theoretically that higher wage dispersion lower labor market participation as a negative side-effect. Empirical analyses support this result. A higher regional wage level as well as low unemployment as an indicator for the stability of jobs come along with high participation. A rise in wage dispersion in the lower part of the wage distribution is connected with decreasing employment participation, in the upper part with rising employment participation. As a further result it is shown that interdependencies between regions strongly matter. Additionally we highlight stylized facts about the development of wage inequality. We compare the US and Germany countries with high and low wage flexibility respectively based on harmonized micro data. We analyze the hypothesis that rigidities due to institutional influences imply a deformation of the wage distribution in the left tail. Such a characteristic wage compression would have to appear particularly for groups of low wage workers in countries like Germany. The comparison with the US labor market suggests the assumption that the deformation of the German wage structure with negative impacts on employment is a distorted picture. A further topic addresses the consequences of setting bounds to the extending inequality in the lower part of the wage distribution by introducing a wage floor. We focus on the effects of a minimum wage on wage inequality and employment. This minimum wage was introduced in 1997 in the German construction sector related to the German Workers Posting Law. We find positive wage effects of the minimum wage regulation in Eastern as well as in Western Germany, albeit the wage reaction in Eastern Germany was considerably larger. When it comes to employment effects, negative effects arise for Eastern Germany and positive for West Germany, although the latter are not always statistically significant. This result shows that a binding minimum wage does not necessarily imply negative employment effects. Finally, this contribution deals with a specific aspect of the wage inequality, the gender pay gap. The focus here is on the influence of the regional context. Having controlled for differences in individual characteristics, education and work places between men and women we show that the gender-specific wage differential is considerably higher in rural than in metropolitan areas. This differential has decreased notably in the last three decades in both regional types. The pay gap between young women and men in rural areas, in an environment with low firm density, is almost constantly ten percentage points higher during the whole observational period than in metropolitan settings. This result is consistent with a theoretical model that additionally takes into account market power of firms." (Author's abstract, IAB-Doku) ((en))
"In Großstädten ist das allgemeine Lohnniveau für junge (Vollzeit-)Beschäftigte (im Alter von 25 bis 34 Jahren) mit niedriger oder mittlerer Qualifikation bedeutend höher als in ländlichen Gebieten. ...Dies gilt für Frauen wie für Männer. Aber noch immer werden junge Frauen geringer entlohnt als ihre männlichen Kollegen. Dabei ist der Lohnabstand zwischen Frauen und Männern auf dem Land deutlich höher als in Großstädten. Obwohl in diesen beiden untersuchten Regionstypen die unerklärte geschlechtsspezifische Lohnlücke (Gender Pay Gap) für junge Arbeitnehmer über die letzten dreißig Jahre (Untersuchungszeitraum 1975 bis 2004) hinweg deutlich geschrumpft ist, verharrt der Abstand zwischen beiden nahezu konstant bei rund 10 Prozentpunkten. Für eine Angleichung der geschlechtsspezifischen Lohnunterschiede zwischen Stadt und Land gibt es keinerlei Hinweise." Die Untersuchung enthält quantitative Daten. Forschungsmethode: empirisch; Längsschnitt. Die Untersuchung bezieht sich auf den Zeitraum 1995 bis 2004. (Autorenreferat, IAB-Doku).
"This Brief Report investigates regional differences in the gender pay gap in Western Germany from 1975 to 2004. For this purpose we compare young workers with low and intermediate skill levels employed full-time in rural areas with those in metropolitan areas. In general, the gender pay gap has declined considerably in both areas since 1975. However, compared to big cities, the gender pay gap is considerably higher in regions with low population density. At roughly ten percentage points, the difference between the two types of regions has remained surprisingly constant over the last three decades." Die Untersuchung enthält quantitative Daten. Forschungsmethode: empirisch; Längsschnitt. Die Untersuchung bezieht sich auf den Zeitraum 1995 bis 2004. (author's abstract, IAB-Doku).
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