A mouse model for latent tuberculosis

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Latent tuberculosis (TB) represents a significant global health challenge, with millions harboring Mycobacterium tuberculosis (Mtb) without active disease.
• Current murine models often lack long-term stability or spontaneous reactivation, limiting their utility in studying latent infection dynamics.
• Understanding latent TB is crucial for developing effective strategies to prevent reactivation and transmission.

Purpose of the Study:

• To establish a reproducible and stable murine model for latent tuberculosis.
• To define operational criteria for latent murine TB, including stable bacterial counts and absence of clinical/histopathological signs.
• To evaluate the potential for spontaneous reactivation and the efficacy of a corticosteroid challenge for reactivation.

Main Methods:

• B6D2F1Bom mice were inoculated with varying doses of Mycobacterium tuberculosis via intraperitoneal (i.p.) or intravenous (i.v.) routes.
• Mice were monitored long-term (up to 107 weeks) without anti-TB drug treatment.
• Microbiological (bacterial counts in lungs/spleens) and histopathological analyses were performed.
• Corticosterone was administered to assess reactivation potential.

Main Results:

• Mice infected i.p. with 4 x 10(4) and 4 x 10(5) Mtb bacilli exhibited stable bacterial loads in lungs and spleens.
• These mice showed no clinical signs or significant histopathological changes, fulfilling the criteria for latent infection.
• No spontaneous reactivation was observed during the extended observation period.
• Corticosterone challenge was used to test reactivation potential.

Conclusions:

• A reproducible murine model for latent tuberculosis has been established, characterized by stable Mtb persistence without active disease.
• This model provides a valuable platform for investigating the host-pathogen interactions during latent TB and for testing novel therapeutic strategies.
• Further research can explore mechanisms of Mtb persistence and the transition from latent to active disease using this model.