Host immunosenescence compromises Mycobacterium tuberculosis clearance

Area of Science:

• Immunology
• Gerontology
• Infectious Diseases

Background:

• Immunosenescence, or immune system aging, increases susceptibility to infections like tuberculosis (TB) in older adults.
• Effective containment of Mycobacterium tuberculosis (Mtb) is hindered in elderly individuals during treatment.
• Understanding age-associated immune alterations is crucial for developing improved therapeutic strategies for TB in the elderly.

Purpose of the Study:

• To investigate immunopathology and immune cell function in aged mice infected with Mtb and treated with standard anti-TB drugs.
• To identify cellular and molecular mechanisms underlying delayed Mtb clearance in older individuals.

Main Methods:

• C57BL/6 mice of different age groups (young, old, aged) were infected with Mtb H37Rv via low-dose aerosol.
• Mice received rifampicin and isoniazid (RIF-INH) treatment.
• Mycobacterial load, immune cell populations (T-follicular cytotoxic-like cells), and proteomic analysis of CD4+ T cells were assessed.

Main Results:

• Older mice exhibited delayed Mtb clearance from the lungs post-treatment compared to young mice.
• Increased splenic T-follicular cytotoxic-like cells were observed in Mtb-infected old mice.
• Proteomic analysis indicated deregulated mitochondrial proteins in CD4+ T cells from older mice, suggesting impaired mitochondrial function.

Conclusions:

• Age-associated immune alterations disrupt immunometabolic pathways, contributing to delayed Mtb clearance.
• Targeting immunometabolic dysfunction presents a promising strategy to enhance TB treatment efficacy in older populations.
• This research highlights the need for age-specific therapeutic approaches for tuberculosis.