Genetic models of latent tuberculosis in mice reveal differential influence of adaptive immunity. Academic Article uri icon

Overview

abstract

  • Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of biotin protein ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established. TrxB2 depletion resulted in a latent infection that required adaptive immunity for control and reactivated with high frequency, whereas latent infection after BPL depletion was independent of adaptive immunity and rarely reactivated. We identified immune signatures of T cells indicative of relapse and demonstrated that BCG vaccination failed to protect mice from TB relapse. These reproducible genetic latency models allow investigation of the host immunological determinants that control the latent state and offer opportunities to evaluate therapeutic strategies in settings that mimic aspects of latency and TB relapse in humans.

publication date

  • July 16, 2021

Research

keywords

  • Adaptive Immunity
  • Latent Tuberculosis
  • Mycobacterium tuberculosis
  • Tuberculosis

Identity

PubMed Central ID

  • PMC8289691

Scopus Document Identifier

  • 85110593302

Digital Object Identifier (DOI)

  • 10.1084/jem.20071367

PubMed ID

  • 34269789

Additional Document Info

volume

  • 218

issue

  • 9