title: A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread.
abstract: 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.
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. kastenmullerw@mail.nih.gov
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
authors.forename: Parizad
authors.initials: P
authors.lastname: Torabi-Parizi
authors.forename: Naeha
authors.initials: N
authors.lastname: Subramanian
authors.forename: Tim
authors.initials: T
authors.lastname: Lämmermann
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D008196:Lymph / Q000382:microbiology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012874:Skin Diseases, Infectious / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D007371:Interferon-gamma