Biophysical mechanisms of tissue invasion and parasite trapping in a mouse model of hookworm infection

• Applicants: Professor Dr. David Vöhringer; Professor Vasily Zaburdaev, Ph.D.
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551748372

Estimated 700 million people are affected by hookworm infections world-wide leading to major socioeconomic problems and a pronounced health impact caused by anemia, malnutrition and growth retardation of children. While medications can reduce worm burden they are often of low efficiency due to reinfections and may lead to the emergence of drug resistance. The natural mouse helminth Heligmosomoides polygyrus bakeri (Hpb) is a frequently used laboratory model to study the mechanisms of hookworm infections including pathways of protective immunity in mice. Worm larvae ingested by mice invade the small intestine were they stay for a week in granuloma-like structures to mature to adult worms, then exit to the intestinal lumen and begin to reproduce, often leading to a chronic infection. Physical forces, playing central roles in the processes of larval migration and invasion to the submucosa, maturation in granuloma-like structures and their final escape into the intestinal lumen, are poorly defined. Importantly, these processes differ dramatically between primary and secondary infections, indicating a complementary role of the immune response from the host: upon secondary infection larvae get efficiently trapped in granulomas. The mechanism(s) leading to larval trapping are not well understood. We hypothesize that the biophysical properties of Hpb larvae, host tissue, and larvae-host interactions determine the course of infection. We will combine in vivo imaging and modern biophysical tools to measure forces and material properties with advanced statistical analysis and modeling to address this hypothesis. Therefore, motility and larval forces during initial tissue invasion and inside granulomas, mechanical properties of encapsulating granulomas and how those change with immunological status of the host are at the focus of this proposal. Our results would yield the first comprehensive characterization of the role of physical parameters in host-helminth interactions that could lead to development of new treatment strategies against helminth infections

• DFG Programme: Priority Programmes
• Subproject of: SPP 2332: Physics of Parasitism