Sorting nexin 5 mediates antigen presentation and immunity against Mycobacterium tuberculosis

Area of Science:

• Immunology
• Cell Biology
• Infectious Diseases

Background:

• Tuberculosis (TB) is a major global infectious disease.
• Host immune pathways regulating Mycobacterium tuberculosis (Mtb) infection are not fully understood.
• Sorting nexin 5 (SNX5) is involved in endosomal trafficking and immunity, but its role in TB is unknown.

Purpose of the Study:

• To investigate the role of SNX5 in host immunity during Mtb infection.
• To determine how SNX5 influences lung inflammation and antigen presentation in TB.

Main Methods:

• Used SNX5-deficient mice and wild-type mice for low-dose aerosol Mtb infection.
• Analyzed lung inflammation, bacterial burden, immune cell recruitment, and macrophage function.
• Assessed MHC class II antigen presentation, antigen degradation, peptide loading, and CD4+ T cell activation.

Main Results:

• SNX5-deficient mice showed increased mortality and exacerbated lung inflammation despite similar bacterial loads.
• SNX5 deficiency impaired MHC class II antigen presentation by reducing antigen degradation and peptide loading.
• Reduced antigen presentation led to impaired activation of antigen-specific CD4+ T cells.

Conclusions:

• SNX5 is a novel regulator of MHC class II peptide loading during Mtb infection.
• The endosomal sorting machinery, via SNX5, plays a critical role in immunity to intracellular pathogens.
• SNX5 influences inflammatory outcomes in pulmonary TB.