Host-pathogen interactions
Interactions with lung epithelium
Mtb primarily infects the airways, however very little is known on the response of the airway epithelium to mycobacterial species. We hypothesize that the initial innate response of the epithelium is critical in shaping subsequent immune responses. We investigate the response of airway and alveolar epithelial cells to mycobacterial exposure in collaboration with Prof Pieter Hiemstra and Dr Anne van der Does of the department of Pulmonology.
Assessment of granuloma architecture
Granuloma formation is one of the key hallmarks of mycobacterial infections. However the spatial organization of granulomas in the lung is relatively unknown and limited to low dimensional data. Therefore, we currently explore granuloma organization, with focus on the key immune players, with high-dimensional imaging mass cytometry.
Characterization of effector responses (oa MGIA)
Protective immune responses against mycobacteria have not been fully characterized. We employ functional assays, in particular the Mycobacterial Growth Inhibition Assay (MGIA), to characterize immune responses that mediate the protective responses. Combination of functional data with extensive spectral flow cytometry, cytokine assessments as well as transcriptomic data sets provides important new players to be targeted in future vaccination strategies.
HDT
Identification of targets
In the combat against drug-resistant strains of
mycobacteria we investigate host-directed therapies
as novel therapeutic strategy. Intracellular bacteria
exploit many strategies to facilitate their intracellular
survival by so called host-pathogen interactions.
Better understanding of these host-pathogen
interactions will facilitate design of host-directed
therapies, which by definition counteract or alleviate
these pathogen-beneficial interactions to facilitate eradication of the invading pathogen. As host-directed therapies target host intracellular proteins, it is unlikely that the pathogens develop resistance against these compounds.
Identification of compounds
In our search for novel (host-directed) therapies extensive libraries of compounds are screened, when compounds with successful anti-bacterial activity are identified, we explore their mechanism of action. At present, libraries of compounds, including possible repurposable drugs are screened in vitro and in zebrafish models for their efficacy against Mtb. We have a long-standing collaboration with the Institute for Biology at Leiden University as well as with multiple industrial partners.
One Health
Besides around Population- and Global Health, our research into Leprosy and TB evolves also around One Health: insight into environmental and zoonotic sources of mycobacteria, are particularly important to dissect routes of transmission preventing leprosy elimination. For this purpose, we investigate animals, soil, water and centuries old skeletons for the presence of M. leprae DNA. Furthermore, assessment of antibodies against M. leprae is used to detect infection in red squirrels and armadillos.
Bovine TB, caused by M. bovis, can cause zoonotic TB, particularly in LMIC. Together with the research group of Prof. Jayne Hope (University of Edinburgh) we investigated with which markers and what tests, M. bovis infected animals can be discriminated from BCG vaccinated animals for improvement of veterinary health.
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