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

• Published in: Cell 2012-09, Vol.150 (6), p.1235-1248
• Main Authors: Kastenmüller, Wolfgang, Torabi-Parizi, Parizad, Subramanian, Naeha, Lämmermann, Tim, Germain, Ronald N.
• Format: Article
• Language: English
• Subjects: Animals; antibiotic resistance; antigens; bacteria; Bacterial Infections - immunology; CD8-positive T-lymphocytes; cell communication; Host-Pathogen Interactions; Immunity, Innate; Inflammasomes - metabolism; innate immunity; Interferon-gamma - immunology; interleukin-18; Interleukin-18 - immunology; Lymph - microbiology; lymph nodes; Lymph Nodes - cytology; Lymph Nodes - immunology; macrophages; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; natural killer cells; pathogens; secretion; Skin Diseases, Infectious - immunology; Specific Pathogen-Free Organisms; T-Lymphocytes - immunology; Virus Diseases - immunology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2012.07.021

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 (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. [Display omitted] [Display omitted] ► 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 A network of diverse lymphoid cells are spatially prepositioned close to sentinel macrophages lining the lymph nodes where they can rapidly and efficiently receive cytokine signals from the pathogen-sensing phagocytes, thus blocking the dissemination of bacteria and viruses that attempt to hijack the lymphatic network.