CD44 receptor targeted nanoparticles augment immunity against tuberculosis in mice

Area of Science:

• Immunology
• Microbiology
• Nanotechnology

Background:

• Tuberculosis (TB) remains a significant global health challenge, necessitating novel therapeutic strategies.
• Host-defense mechanisms against Mycobacterium tuberculosis (Mtb) are complex and incompletely understood.
• CD44-mediated signaling plays a potential role in macrophage (MФ) immune responses.

Purpose of the Study:

• To investigate the role of CD44-mediated signaling in host defense against TB.
• To design and evaluate CD44-targeting liposomes (CD44TA-LIP) as a potential vaccine to enhance anti-TB immunity.

Main Methods:

• Utilized a mouse model of TB and Mtb-infected human macrophages (MФ).
• Developed liposomes targeting CD44 via thioaptamers (CD44TA-LIP).
• Assessed Mtb killing, cytokine production, antigen presentation, T-cell activation, nitric oxide, and defensin production in vitro and in vivo.

Main Results:

• CD44TA-LIP enhanced Mtb killing in MФ, increasing pro-inflammatory cytokines (IL-1β, TNF-α, IL-12) and nitric oxide production.
• Activated MФ showed enhanced MHC-II antigen presentation and CD4 T-cell activation.
• Intranasal CD44TA-LIP administration in mice reduced Mtb load by tenfold and increased specific T-cell populations.
• Biodistribution studies showed preferential lung accumulation of CD44TA-LIP with no observed toxicity.

Conclusions:

• CD44-mediated signaling is crucial for host defense against TB.
• CD44TA-LIP demonstrates significant therapeutic potential as a novel vaccine strategy for TB.
• Targeting CD44 offers a promising avenue for boosting host immunity against Mtb infection.