Early in vivo infection dynamics in non-human primates infected with Mycobacterium tuberculosis (MPF3P.813)

Abstract

Abstract Tuberculosis (TB) continues to pose a significant health risk to morbidity and mortality worldwide. The vast majority of individuals infected with M. tuberculosis, the causative agent of TB, contain the infection as clinically asymptomatic latent TB. A small minority of people do not and either present with primary active disease or reactivate over their lifetime. By examining early events in infection at the local lesion level, we aim to uncover some of the basis for the observed spectrum of TB disease and host outcome. Using genetically barcoded M. tuberculosis, serial PET/CT lesion imaging, and tools to analyze each granuloma at the microbial and immunological level, we are tracking local lesion development and dissemination at various stages of infection in cynomolgus macaques. Background studies have revealed that granulomas are dynamic entities that largely arise from single bacteria. We hypothesize that early interactions between M. tuberculosis and host immune components contribute to lesion heterogeneity and that these initial events influence infection outcome. We performed a small reinfection experiment with M. tuberculosis barcoded strains. Our data suggests that primary infection limits secondary infection lesion development and dissemination. Further analysis of this study is ongoing. Probing the mechanisms that underlie the human TB spectrum will reveal crucial stages of infection that can be exploited for novel therapeutic design.