Macrophage-T cell interactions promote SLAMF1 expression for enhanced TB defense.

CD4+ T cells are crucial for protective immunity to intracellular pathogens. In addition to secreting cytokines, CD4+ T cells promote control of Mycobacterium tuberculosis infection through cognate interactions with macrophages, but the mechanism has been unclear. Here, we show that SLAMF1/CD150 is highly and uniquely induced in macrophages by antigen-specific interactions with CD4+ T cells. In macrophages, SLAMF1 enhances the generation of reactive oxygen species and restricts Mtb replication. Mtb-infection of mice promotes SLAMF1 expression specifically on infected macrophages, not uninfected bystanders. SLAMF1 expression depends on adaptive immunity and also autophagy. Moreover, Slamf1 mice have higher Mtb burden and more rapid disease progression than wild type mice. Using Slamf1 conditional knock-out mice, we show that in vivo Slamf1 is specifically required in macrophages to restrict mycobacterial growth and limit IL-1β production. In macaques, macrophage SLAMFI expression also correlates with T cell responses and protection. Combined, these data demonstrate that SLAMF1 is a marker of macrophage-T cells interactions, and it promotes protection against Mtb.