T cell–macrophage interactions in tuberculosis: What we've got here is failure to communicate

Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality, and the development of a new, highly effective vaccine would have a tremendous beneficial impact on global health. Although conventional memory CD4 and CD8 T cells will likely be key mediators of long-lived, vaccine-elicited protection, a potent T cell-inducing vaccine against TB has been elusive. Protection by Mycobacterium tuberculosis (Mtb)-specific T cells is mediated primarily through their communication with Mtb-infected macrophages. Here, we discuss emerging evidence of multiple structural and immunoregulatory factors that limit effective T cell-macrophage interactions in TB granulomas, posing a unique challenge to vaccine-induced protection. Developing new TB vaccination strategies will require a better understanding of the crosstalk between T cells and infected pulmonary macrophages and strategies to enhance these interactions.