Sorting nexin 5 deficiency impairs MHC class II antigen presentation and inflammatory responses during tuberculosis

Area of Science:

• Immunology
• Cell Biology
• Infectious Diseases

Background:

• Tuberculosis (TB) is a major global infectious disease caused by Mycobacterium tuberculosis (Mtb).
• Host immune responses, including antigen presentation and inflammation, are critical for controlling Mtb infection but are not fully understood.
• Sorting nexin 5 (SNX5) is involved in endosomal trafficking and antigen processing, but its role in antibacterial immunity is unknown.

Purpose of the Study:

• To investigate the role of SNX5 in host defense against Mtb infection.
• To determine if SNX5 influences antigen presentation and lung inflammation during Mtb infection.

Main Methods:

• Mice deficient in SNX5 (Snx5-/-) were infected with Mtb via low-dose aerosol.
• Pulmonary bacterial burden, lung inflammation, immune cell recruitment, and macrophage function were assessed.
• Major histocompatibility complex (MHC) class II antigen presentation and CD4+ T cell activation were analyzed in vitro.

Main Results:

• SNX5-deficient mice showed increased mortality and exacerbated lung inflammation despite similar bacterial loads compared to wild-type mice.
• SNX5 deficiency impaired MHC class II antigen presentation in macrophages by affecting endolysosomal proteolysis.
• Reduced MHC class II antigen presentation led to decreased activation of antigen-specific CD4+ T cells.

Conclusions:

• SNX5 is essential for efficient MHC class II antigen presentation during Mtb infection.
• SNX5 regulates inflammatory outcomes in the lungs during tuberculosis.
• Targeting SNX5 may offer new strategies for managing TB.