Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis
| Autor: | Courtney R. Plumlee, John D. Aitchison, Louis J. Picker, Jared L. Delahaye, Michael Y. Gerner, Scott G. Hansen, Tige R. Rustad, Kevin B. Urdahl, Caleb R. Stoltzfus, Benjamin H. Gern, Vitaly V. Ganusov, Sara B. Cohen, Michael K. Axthelm, Daniel E. Zak, David R. Sherman, Fergal J. Duffy |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Tuberculosis
Ultra low dose Disease Microbiology Article Mycobacterium tuberculosis Mice 03 medical and health sciences 0302 clinical medicine Virology Active tb medicine Animals Humans RNA-Seq Lung Tuberculosis Pulmonary 030304 developmental biology 0303 health sciences Granuloma biology biology.organism_classification medicine.disease Macaca mulatta Bacterial Load Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Immunology Disease Progression Female Parasitology Biomarkers 030217 neurology & neurosurgery Bacteria |
| Zdroj: | Cell Host Microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2020.10.003 |
| Popis: | Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1–3 founding bacteria, reflecting a physiologic inoculum. ULD-infected mice exhibited highly heterogeneous bacterial burdens, well-circumscribed granulomas that shared features with human granulomas, and prolonged Mtb containment with unilateral pulmonary infection in some mice. We identified blood RNA signatures in mice infected with an ULD or a conventional Mtb dose (50–100 CFU) that correlated with lung bacterial burdens and predicted Mtb infection outcomes across species, including risk of progression to active TB in humans. Overall, these findings highlight the potential of the murine TB model and show that ULD infection recapitulates key features of human TB. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|