Sorting nexin 5 is necessary for MHC Class II antigen presentation and host defense against Mycobacterium tuberculosis infection.

Sorting nexin 5 (SNX5) is a phox homology (PX) and bin, amphiphysin, rvs (BAR) domain protein best known for roles in endosomal trafficking, antigen processing, and antiviral host defense, but its contribution to immunity during Mtb infection is unknown.

Here, we show that SNX5-deficient mice exhibit markedly increased mortality following low-dose aerosol infection despite unchanged pulmonary bacterial burden compared to wild-type mice. Snx5-/- mice developed exacerbated lung inflammation without major alterations in immune cell recruitment. In macrophages, Snx5-/- did not affect phagocytosis, vacuolar maturation, intracellular bacterial control, or global transcriptional responses to Mtb, but was required for efficient MHC class II antigen presentation.