SLAMF1 is regulated by macrophage-CD4 T cell contact and confers protection to Mycobacterium tuberculosis

CD4 T cells are crucial for protective immunity to Mycobacterium tuberculosis (Mtb). Because CD4 T cell protection depends upon direct interaction with infected macrophages, we sought to identify contact-dependent protective factors. We discovered that direct contact with antigen-specific CD4 T cells drives signaling lymphocytic activation molecule family member 1 (SLAMF1/CD150) expression on macrophages. SLAMF1 is a cell-surface receptor that mediates homotypic interactions between hematopoietic cells, interacts with microbes, and promotes macrophage antimicrobial responses. In mice, SLAMF1 expression was induced on Mtb-infected myeloid cells in a T cell-dependent manner and partially impaired in autophagy-deficient macrophages. In non-human primates, antigen presentation by lung macrophages induced SLAMF1 expression in a manner that correlated with T cell abundance and vaccine protection. Finally, in mice SLAMF1 limited Mtb burden and inflammatory responses during Mtb infection. We conclude that SLAMF1 is a T cell contact-dependent factor in macrophages that contributes to host protection from TB.