The C3HeB/FeJ Kramnik mouse as a model to investigate the efficacy of therapeutic tuberculosis interventions

Abstract

Tuberculosis (TB) remains a formidable global health challenge, classified as the leading infectious disease killer, driven by the increasing prevalence of multidrug-resistant Mycobacterium tuberculosis strains. This persistent threat not only overwhelms public health infrastructures but also deepens socio-economic inequalities worldwide, underscoring the urgent need for novel therapeutic strategies. The C3HeB/FeJ Kramnik mouse model, frequently used for its capacity to mimic human-like granulomatous lesions, has emerged as a pivotal tool in TB research. However, despite its advantages, the model has limitations, particularly in terms of macrophage pathology and restricted B-cell activity, which pose significant hurdles for translating preclinical findings into human applications. By developing models that better reflect human immune responses, the translation of findings into clinical applications may be improved, ultimately leading to more effective TB treatments and vaccines. This study aims to evaluate the Kramnik model by investigating the efficacy of a novel Pheroid(R) formulation containing traditional TB therapeutics in the C3HeB/FeJ Kramnik mouse model. The potential and limitations inherent to the Kramnik model are explored and the need for complementary genomic analyses, such as sequencing SP110 and SP140, to elucidate the susceptibility linked to the SST1 locus is illustrated. In addition, this article attempts to serve as a critical evaluation of the inherent limitations of current animal models like the Kramnik model, with the aim of paving the way for more accurate and reliable translational research in the fight against TB.