The aim of the research is to understand the molecular and cellular immunological basis of host parasite interaction with particular emphasis on chronic helminth infections and malaria.
Main research themes
The immunology of host parasite interaction is studied :
- to be able to understand immunity to malaria parasites and helminths and thus serve vaccine development
- to characterize immunologically and metabolically how parasites skew immune responses towards pro-inflammatory or anti-inflammatory state
- to learn how parasites exert immunoregulatory responses and thereby have beneficial effect on the development of allergic disorders and type 2 diabetes
- to delineate how the rural to urban transition in many low- to middle-income countries, associated with loss of parasites, affects the immune system and thereby affects vaccine responses as well as prevalence of diseases such as asthma and type 2 diabetes
Immunity to malaria parasites and helminths to serve vaccine development
The development of immunity to malaria parasites, schistosomiasis and hookworm infections is studied in animal models, in populations living in malaria endemic regions as well as in controlled human infection models. Utilising the flow cytometry unit of LUMC as well as state of the art technologies such as glycan arrays, and mass cytometry, we are generating high dimensional data which identifies humoral and cellular responses that correlate with either natural immunity that develops with increasing exposure, or vaccine induced immunity.
Skewing of immune responses by parasites
The skewing of immune responses are studied in vitro using co culture of T cells, B cells, Dendritic cells and macrophages with parasite extracts or single parasite derived molecules. In vivo murine models using specific gene knock outs, are establishing the molecular pathways that are involved in the development of Type-1, Type-2, Type-17 and regulatory immune responses. There is a recent focus on the characterization of the cellular metabolism that affects immune response skewing by using technologies such as the seahorse and metabolomics platforms at the LUMC.
Immunoregulation by parasites and effect on asthma and type 2 diabetes
Helminths ensure their long term survival within their host by inducing immunoregulatory responses. These are characterized by regulatory T and B cells as well as regulatory DCs or macrophages. The same regulatory responses that benefit the parasites, seem to also benefit the host when it comes to the development of allergic disorders or type 2 diabetes. Animal models developed to study the effect of schistosome infections on asthma and type 2 diabetes are identifying immunological and non-immunological pathways that can be targeted for novel therapeutics. The identification of single molecules from schistosomes and their expression in plants is allowing the precise mapping of the moieties, such as glycans, that can play a role in modulating the immune system to harness diseases such as asthma and type 2 diabetes.
Rural to urban transition and immunological responses
Disease patterns are extremely polarized, whereas a large proportion of the population in rural areas suffer from parasitic diseases, the rich in large urban centers, face diabetes, cardiovascular and allergic diseases.
Moreover, there is increasing awareness that responses to vaccines can how geographical variation, not explained by genetic factors. The loss of parasites upon urbanization, might play an important role in the polarized disease profiles or variation in vaccine responses, through changes in the immune system. The immune system of a person living in rural areas of Gabon or Senegal looks very different from those that have no history of exposure to parasitic infection. The characterization of the populations living in rural areas, through collaboration with institutions in LMIC, such as CERMEL in Gabon, UI and UnHas in Indonesia and comparing them with those living in urban setting, taking systems biology approaches should help the development of new interventions that might slow down or prevent the epidemic of allergic disorders or diabetes while at the same time improve vaccine responses.