Immunodynamics of polyparasitism (360G-Wellcome-109327_Z_15_A)

Gastrointestinal (GI) nematode infection is one of the most common infections of man’s poorest communities (circa 2 billion). Infections are acquired early in life, chronic in nature and acquired immunity is slow to develop and incomplete leading to life long infection. This provides an infectious background that influences all aspects of health and disease. Co-infection by more than one species of GI nematode is the norm. Our current knowledge of mechanisms of resistance and susceptibility to these infections has come from well-defined laboratory model systems using single bolus high dose infections by single parasite species where sterile immunity can be generated. The present proposal will utilize two of the most immunologically well defined laboratory systems to identify mechanisms of resistance generated by more natural infection exposure i.e. repeated low dose trickle infection during concurrent infection by two nematode species reflecting those concurrently infecting man. The project is designed to identify the critical components of the immune response that influence resistance generated "naturally" to GI nematodes, from the myriad of mechanisms proposed from current laboratory studies. This will help define new and better models for future studies and a rigorous setting for developing effective control strategies such as vaccines.