CXCR5 expressing T helper cells mediate protective immunity against tuberculosis

One third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we show that organized ectopic lymphoid structures containing CXCR5+ T cells are found in Mtb-infected lungs. In addition, we show that in experimental Mtb infection models, the presence of CXCR5 + T cells inside ectopic lymphoid structures are associated with immune control. Furthermore, in a mouse model of Mtb infection, we show that activated CD4+ CXCR5+ T cells accumulate in Mtb-infected lungs, and produce proinflammatory cytokines. Absence of CXCR5 in mice results in increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We show that CXCR5 expression on T cells mediates correct T cell localization within TB granulomas, efficient macrophage activation, promoting protection against Mtb infection and facilitating lymphoid follicle formation. These data show a novel role for CD4+ CXCR5 + T cells in protective immunity against TB and highlight their potential use for future TB vaccine design and therapy.