Author:
Joslyn Louis R.,Flynn JoAnne L.,Kirschner Denise E.,Linderman Jennifer J.
Abstract
AbstractSome persistent infections provide a level of immunity that protects against reinfection with the same pathogen, a process referred to as concomitant immunity. To explore the phenomenon of concomitant immunity during Mycobacterium tuberculosis infection, we utilized HostSim, a previously published virtual host model of the immune response following Mtb infection. By simulating reinfection scenarios and comparing with data from non-human primate studies, we propose a hypothesis that the durability of a concomitant immune response against Mtb is intrinsically tied to levels of tissue resident memory T cells (Trms) during primary infection, with a secondary but important role for circulating Mtb-specific T cells. Further, we compare HostSim reinfection experiments to observational TB studies from the pre-antibiotic era to predict that the upper bound of the lifespan of resident memory T cells in human lung tissue is likely 2–3 years. To the authors’ knowledge, this is the first estimate of resident memory T-cell lifespan in humans. Our findings are a first step towards demonstrating the important role of Trms in preventing disease and suggest that the induction of lung Trms is likely critical for vaccine success.
Funder
National Institutes of Health
Office of Extramural Research, National Institutes of Health
Wellcome Leap DeltaTissue Program
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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