Parasitism is the strongest force in evolution. Throughout evolution, infectious organisms have acquired adaptive advantages that allowed them to coexist with their hosts. Some of these strategies involve mimicking central mechanisms that regulate immune detection by the host immune system. We hypothetize that autoantibodies largely result from an evolutionary adaptation of human pathogens to perturb the host immune responses and divert immune defenses. In this project, we are systematically identifying and validating occurrences of molecular mimicry between pathogen proteins and human immune molecules, and defining how these events affect immunity to subsequent infections. This project employs a series of immune-based approaches using patient plasma, protein lysates of human pathogens, affinity binding, and competitive assays, genome editing techniques, and experimental infections in vivo. This project will contribute to our understanding of the mechanisms driving autoimmunity and susceptibility to opportunistic infections.
