Infection Biology

We aim to understand, reduce and treat infections in humans and animals

Humans and animals are colonised by and exposed to a large variety of bacteria and viruses. The interaction of bacteria and viruses with their host and with each other is complex but very important in health and disease processes. In the Infection Biology group, we study microbe-host and virus-host interactions at the molecular, (sub)cellular and tissue level. We connect knowledge and research lines in the area of microbe/virus-host interactions at mucosal surfaces, bacterial/viral coinfections and the role of extracellular vesicles during healthy mucosal maintenance, inflammation and carcinogenesis.

We aim to better understand the underlying molecular mechanisms of bacterial/viral interactions with their hosts and host defenses. These novel insights can be used to inspire clinical applications that restore commensal interactions or prevent or cure pathogenic infection.

Microbe-host interactions at mucosal surfaces

Microbial communities or microbiota interact with human and animal hosts at mucosal surfaces. Commensal bacteria contribute to a healthy mucosa in the intestine, respiratory tract and vagina, but pathogens have developed the ability to colonise and invade. The mucus layer that covers all these mucosal surfaces protects the host against pathogenic invasion by bacteria such as Salmonella enterica, Escherichia coli in the intestine or Streptococcus pneumoniae in the respiratory tract. It also facilitates colonisation by commensal bacteria such as Bifidobacteria and Lactobacilli. The main building blocks of the mucus layer are large mucin proteins. Gel-forming mucins are secreted by goblet cells and form a viscous gel that covers the epithelium. Anchored transmembrane mucins are main regulators of epithelial proliferation, wound healing, barrier function and immune responses. All mucins are densely decorated with diverse structures containing different sugars called glycans. Bacteria can feed on or attach to mucin-specific glycan structures and these interactions play an essential role in mucosal health and disease.

The mucus layer is a black box in infection biology research. We need to understand where, when and how bacteria-mucin interactions impact health and disease.

Dysregulation of bacteria-mucus interactions can lead to diseases including inflammatory bowel disease, vaginal dysbiosis, infertility and enhanced susceptibility to viral and bacterial (co)infections. In our group, we aim to unravel the molecular mechanisms of bacteria-mucin interactions at mucosal surfaces in order to improve human and animal health.

Extracellular Vesicles in infection and immune defense

Extracellular Vesicles (EVs) are nanosized carriers of information produced by cells in all kingdoms of life. During health and (infectious) diseases, these EVs are part of the molecular interactions of human and animal cells, as well as microbes. We have longstanding experience in EV isolation and characterisation and fundamental EV biology. We apply this knowledge to define the role of EVs in host-pathogen communication and immune defense.

Extracellular vesicles need a place in the design of next-generation antiviral and antibacterial treatment strategies

We investigate how picornaviruses and flaviviruses use host EVs to protect them from immune defense mechanisms and support their spreading. We also explore how virus-induced and bacterial EVs may help these pathogens to cross gastrointestinal and vascular barriers. We use high-resolution microscopic and flow cytometric technologies, in-depth  proteomic and transcriptomic analyses, and advanced cell culture models. EVs need a place in the design of next-generation antiviral and antibacterial strategies, and we provide fundamental knowledge to guide this development.

Bacterial adaptation mechanics

Bacteria possess remarkable abilities to sense and adapt to ever-changing physical and chemical environments. This enables them to survive and proliferate under diverse and often hostile conditions, including pressures from host immune responses and antimicrobial agents. Studying these adaptive processes at the molecular and genetic level not only helps us understand bacterial survival strategies but also provides essential avenues for the discovery of new antimicrobial compounds to which bacteria cannot easily adapt. We focus primarily on bacterial adaptation mechanisms involved in pathogenesis and investigate antimicrobial compounds to which bacteria cannot adapt.

Studying bacterial adaptation reveals new paths to antimicrobials that resist resistance

Advanced Cell Culture Facility

To perform cutting-edge veterinary biomedical research, it is essential to have access to in vitro tissues that closely resemble the in vivo tissues of different animals. At the Division of Infectious Diseases and Immunology, we provide a facility for the harvesting, biobanking and culturing of primary epithelial, stromal and immune cells from different animal species. Our expertise includes tissues from respiratory, nasal, urogenital and intestinal origins.

Advanced species-specific primary cell culture systems can play a key role in reducing animal experimentation

The methods we use include seeding of cells and differentiation of tissues from farm and companion animals in transwell systems under air-liquid interface (ALI) and liquid-liquid interface (LLI) conditions. We are also developing methods for culturing veterinary tissue explants and organoid cultures. Our advanced cell culture models are suitable to study species-specific infection dynamics of viral (Influenza A virus) and bacterial pathogens (Salmonella, Mannheimia, Campylobacter) with readout parameters including barrier integrity (TEER), cytotoxicity (LDH) and visualisation of bacteria, viruses and relevant host receptors by confocal immunofluorescence, FISH and immunohistochemistry.

Interested in working with us? Please contact Albert van Dijk (a.vandijk1@uu.nl).

Staff members