A Spatially-Organized Multicellular Innate Immune Response in Lymph Nodes Limits Systemic Pathogen Spread

SummaryThe 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 (natural killer cells, γδ T cells, natural killer T cells, and innate-like CD8+ T cells) are spatially prepositioned 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 antimicrobial 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.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (5006 K)

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (308 K)Download as PowerPoint slideHighlights► Spatial and functional organization in lymph nodes prevents systemic pathogen spread ► A macrophage-lymphocyte communication loop promotes innate immune host defense ► Innate effectors are prepositioned close to macrophages to rapidly produce IFNγ ► Inflammasome-generated IL-1 and IL-18 activate and orchestrate the innate defense