TB immunopathology across the M. tuberculosis infection and TB disease spectrum

Tuberculosis claims ~1.3 million lives and >10 million develop tuberculosis each year. An efficacious vaccine is needed to improve tuberculosis control. However, a poor understanding of host-pathogen interactions and a lack of human immune correlates of protection hinder rational development of interventions. This knowledge gap is primarily due to difficulties inherent in studying a disease caused by an obligate human pathogen residing in inaccessible anatomical sites. By leveraging autopsies on decedents with incidental M. tuberculosis (Mtb) infection or tuberculosis pathology, and applying cutting-edge molecular microbiology and immunological profiling, we will describe the tissue-level spectrum of Mtb infection and tuberculosis disease in pulmonary tissue, determine bacillary presence and viability, and identify the immunological mechanisms that control Mtb in humans. Our team leverages extensive experience in human TB pathology and autopsy programs and surgical cohorts at the African Health Research Institute (AHRI), and the University of Cape Town (UCT). We will examine tissue from individuals who died of non-TB causes and measure immune outcomes with cutting-edge immunological assays to identify responses that associate with successful control of Mtb in lesions. We will generate new knowledge to enhance our understanding of protective immunity, thereby advancing rational design of vaccines and therapeutic strategies.