A review of murine models of latent tuberculosis infection

Abstract

The mechanisms of latency and the causes of reactivation of Mycobacterium tuberculosis remain poorly understood; an important reason for this gap in knowledge is the absence of a standardized animal model of latent tuberculosis infection (LTBI). A complete LTBI model should incorporate 2 aspects of LTBI: a persistent infection model with a low bacterial load and a latent infection model that is modified from the Cornell model. Many parameters must be carefully considered to establish an LTBI model, including the inoculating dose, the route of infection, the time interval between infection and the initiation of antibiotic therapy, and the genetic background of the host animal. The responsiveness of this mouse model of LTBI can be assessed through the integrated use of indices, including Karnofsky performance status, bacterial load in spleen and lungs, induced levels of interferon-gamma and tumour necrosis factor-alpha, expression of interleukin (IL)-10 and IL-4 in tissues, specific antigen load in organs, time required for hormone-induced TB relapse, expression level of dormancy genes, and CD4 T-cell count.