BATF3-dependent dendritic cells drive both effector and regulatory T-cell responses in bacterially infected tissues

The gastric lamina propria of mice that have been experimentally infected with the pathobiont Helicobacter pylori hosts a dense network of myeloid cells that includes BATF3-dependent CD103+ dendritic cells (DCs). We show here that CD103+ DCs are strictly required for gastric Th1 responses to H. pylori and for H. pylori infection control. A similar dependence of type 1 immunity on CD103+ DCs is observed in a Mycobacterium bovis BCG infection model, and in a syngeneic colon cancer model. Strikingly, we find that not only the expansion and/or recruitment of Th1 cells, but also of peripherally induced, neuropilin-negative regulatory T-cells to sites of infection requires BATF3-dependent DCs. A shared feature of the examined models is the strongly reduced production of the chemokines and CXCR3 ligands CXCL9, 10 and 11 in BATF3-deficient mice. The results implicate BATF3-dependent DCs in the recruitment of CXCR3+ effector and regulatory T-cells to target tissues and in their local expansion.
Author summary In this work, Arnold & Zhang et al report that CD103+ DCs are required for protective Th1 responses, infection control of mucosal and systemic bacterial pathogens, and anti-tumor immunity driven by CD4+ Th1 cells and CD8+ T cells. CD103+ DCs further specifically promote the recruitment of Tbet+ peripherally induced Tregs to sites of infection. The results implicate CD103+ DCs in the trafficking of CXCR3+ Tbet+ T-cells to sites of infection and tumorigenesis.