Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages
Ophélie Rutschmann, Chiara Toniolo, John D. McKinney
Abstract
In this report, we demonstrate that fluctuations in the expression of antimicrobial genes can define how single host cells control bacterial infections. We show that preexisting cell-to-cell variation in the expression of a single gene, that for inducible nitric oxide synthase, is sufficient to explain why some macrophages kill intracellular M. tuberculosis while others fail to control bacterial replication, possibly leading to disease progression. We introduce the concept that chance encounters between heterogeneous bacteria and host cells can determine the outcome of a host-pathogen interaction. This concept is particularly relevant for all the infectious diseases in which the number of interacting pathogens and host cells is small at some point during the infection.