Central memory CD8 ؉ T cells (TCM) and effector memory CD8

Summary The lymphatic network that transports interstitial fluid and antigens to lymph nodes constitutes a conduit system that can be hijacked by invading pathogens to achieve systemic spread unless dissemination is blocked in the lymph node itself. Here we show that a network of diverse lymphoid cells (NK cells, γδ T cells, NKT cells, and innate-like CD8+ T cells) are spatially pre-positioned close to lymphatic sinus-lining sentinel macrophages where they can rapidly and efficiently receive inflammasome-generated IL-18 and additional cytokine signals from the pathogen-sensing phagocytes. This leads to rapid IFNγ secretion by the strategically positioned innate lymphocytes, fostering anti-microbial resistance in the macrophage population. Interference with this innate immune response loop allows systemic spread of lymph-borne bacteria. These findings extend our understanding of the functional significance of cellular positioning and local intercellular communication within lymph nodes, while emphasizing the role of these organs as highly active locations of innate host defense.