Although urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas... Show moreAlthough urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas including health. In particular, urban areas in low and middle incomecountries (LMIC), often see a widening gap in economic growth which contributes to healthdisparities between wealthy and underprivileged children. Several studies have establishedthe association between socioeconomic status (SES) and child health, showing that childrenof low-income parents had poorer health status. The rise of non-communicable diseases,the persistence of communicable disease, and the challenge of re-emerging diseases arecurrently a burden in developing countries. Given the rapid increases of urbanization andurban poverty in several developing countries including Indonesia, it is important to elaborateto what extent SES affects child health. We have done so, in relation to outcome of BCGvaccination, atopic sensitization, and intestinal barrier function. We have also investigatedthe interaction between intestinal parasitic infections and bacterial gut microbiota in orderto be able to delineate the contribution of this interaction on the function of intestinal barrier. Show less
Hermans, M.; Roeters van Lennep, J.E.; Daele, P. van; Bot, I. 2019
Mast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which... Show moreMast cells are pluripotent leukocytes that reside in the mucosa and connective tissue. Recent studies show an increased prevalence of cardiovascular disease among patients with mastocytosis, which is a hematological disease that is characterized by the accumulation of mast cells due to clonal proliferation. This association suggests an important role for mast cells in cardiovascular disease. Indeed, the evidence establishing the contribution of mast cells to the development and progression of atherosclerosis is continually increasing. Mast cells may contribute to plaque formation by stimulating the formation of foam cells and causing a pro-inflammatory micro-environment. In addition, these cells are able to promote plaque instability by neo-vessel formation and also by inducing intraplaque hemorrhage. Furthermore, mast cells appear to stimulate the formation of fibrosis after a cardiac infarction. In this review, the available data on the role of mast cells in cardiovascular disease are summarized, containing both in vitro research and animal studies, followed by a discussion of human data on the association between cardiovascular morbidity and diseases in which mast cells are important: Kounis syndrome, mastocytosis and allergy. Show less
The objective of this PhD thesis is to understand mast cell (and basophil) functions and their role in autoimmune disease by focusing on three main aims: 1. To characterize the interaction between... Show moreThe objective of this PhD thesis is to understand mast cell (and basophil) functions and their role in autoimmune disease by focusing on three main aims: 1. To characterize the interaction between innate and Fc receptor triggers on mast cell and basophil function 2. To analyze the interaction between mast cells and CD4+ T cells 3. To understand the function of mast cells in chronic inflammation In this thesis I showed that mast cells can significantly contribute to chronic inflammation through their activation by Fc receptors and TLRs, as well as their interaction with CD4+ T cells, thereby increasing our understanding of their role in allergy and autoimmunity and providing several therapeutic targets to prevent mast cell-mediated immune responses. Show less
In this thesis we reported our investigations of the relationship between soil-transmitted helminths (STH) and a number of outcomes, in particular malaria, insulin resistance (a marker for type-2... Show moreIn this thesis we reported our investigations of the relationship between soil-transmitted helminths (STH) and a number of outcomes, in particular malaria, insulin resistance (a marker for type-2 diabetes (T2D)) and atherosclerosis (a marker for cardiovascular diseases (CVD)) on Flores island, Indonesia. In the study on Flores Island, the use of albendazole as a single dose at three monthly intervals decreased helminth infections significantly. However, this intensive deworming could not eliminate helminth infections. Despite no effect on malaria parasitemia and clinical symptoms was found, we noted that in vitro immune responses were improved after albendazole treatment and significant increases in malaria-specific and mitogen-induced tumor necrosis factor and interferon _ cytokine production were observed. We also reported that helminth infections are associated with improved insulin sensitivity and lower risk factors for CVD. A possible approach to confirm our results will be a long-term, well-powered, placebo controlled (adequate) anthelminthic trials to investigate asymptomatic malaria (in area where clinical malaria is highly prevalent); as well as to study whether alleviation of helminthic pressure is inversely correlated with anti-inflammation, lipid levels and insulin sensitivity, and therefore leads to an accelerated development of T2D and CVD. Show less
Helminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the... Show moreHelminth parasites are able to induce immune regulation in their host. Suppression of the host immune system is beneficial for both the parasite, by inhibiting anti-parasite immunity, and for the host, by preventing tissue damage due to excessive inflammation. There are indications that in countries where parasites have been eliminated the immune regulatory network is impaired, leading to inflammatory diseases such as allergies and asthma. An important player in immune regulation is the regulatory T cell (Treg). We have shown that the number and/or function of Tregs were indeed enhanced in several helminth and also malaria infections in humans. Tregs were not only involved in suppression of anti-parasite responses, but also of responses to other infections or vaccines. We further investigated the effect of helminth elimination in a randomized placebo-controlled trial. Treatment of helminths led to a strong increase in __mainly pro-inflammatory__ immune responses, which confirms the importance of immune regulation during infection. Furthermore, the prevalence of malaria was transiently increased and allergy was slightly on the rise in treated school children. These results further endorse the possible beneficial effects of helminthic therapy, which is currently being tested in a number of clinical trials. Show less
The studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the... Show moreThe studies present in this thesis fall into two broad areas: the first focusing on filarial infection, Ig (immunoglobulin)E levels and risk factors for infection, while the second deals with the possible associations between nematode infection and allergy. Compared to ELISA, RAST is superior in detecting filarial specific IgE in endemic area of Brugia malayi. Levels of filaria-specific IgE and IgG4 in children up to 10 years correlated with maternal antibody levels. Genetic factors had a more pronounced effect in children than in adults. The use of objective measurements, such as skin prick test (SPT) and IgE levels are required when conducting epidemiological studies of allergic diseases in Indonesia. Study on risk factors of allergy in Indonesia showed that nutritional status of children in the high socioeconomic school negatively associate with SPT and IgE positivity but we did not show a statistically significant role for helminths in inhibiting SPT responses. In endemic area of lymphatic filariasis, genetic factors contribute significantly to both total and allergen-specific IgE, whereas environmental factors influence the clustering of SPT positivity. By using several TLR ligands it was demonstrated that the dynamics of cytokine production following the innate immune stimulation can differ according to helminth infection status. Show less
