Infection-Induced Regulation of Natural Killer Cells by Macrophages and Collagen at the Lymph Node Subcapsular Sinus

• Published in: Cell reports (Cambridge) Vol. 2; no. 1; pp. 124 - 135
• Main Authors: Coombes, Janine L., Han, Seong-Ji, van Rooijen, Nico, Raulet, David H., Robey, Ellen A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2012; Elsevier
• Subjects: Accessory cells; Animal models; Animals; Cell activation; Cells, Cultured; Collagen; Collagen - pharmacology; Collagen - physiology; Data processing; Fibers; Infection; Inflammation; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Leukocyte migration; Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymph Nodes - pathology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Macrophages; Macrophages - immunology; Macrophages - pathology; Macrophages - physiology; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Microscopy; Models, Biological; Monocytes; Natural killer cells; Sinus; Toxoplasma - growth & development; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis - immunology; Toxoplasmosis - pathology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2012.06.001

Infection leads to heightened activation of natural killer (NK) cells, a process that likely involves direct cell-to-cell contact, but how this occurs in vivo is poorly understood. We have used two-photon laser-scanning microscopy in conjunction with Toxoplasma gondii mouse infection models to address this question. We found that after infection, NK cells accumulated in the subcapsular region of the lymph node, where they formed low-motility contacts with collagen fibers and CD169+ macrophages. We provide evidence that interactions with collagen regulate NK cell migration, whereas CD169+ macrophages increase the activation state of NK cells. Interestingly, a subset of CD169+ macrophages that coexpress the inflammatory monocyte marker Ly6C had the most potent ability to activate NK cells. Our data reveal pathways through which NK cell migration and function are regulated after infection and identify an important accessory cell population for activation of NK cell responses in lymph nodes. [Display omitted] ► Infection-induced lymph node changes impact natural killer (NK) cell responses ► Following infection, NK cells interact with macrophages near the lymph node capsule ► Inflammatory macrophages activate NK cells ► Interaction with collagen may promote NK cell retention near infection foci The natural killer (NK) cell response to infection is regulated by interactions with cells and components of the extracellular matrix. Robey and colleagues used two-photon laser-scanning microscopy to investigate how these interactions influence NK cell responses to Toxoplasma gondii infection. The authors found that NK cells formed low-motility contacts with collagen fibers and CD169+ macrophages in the subcapsular region of the lymph node, and they show that these interactions regulate NK cell localization and activation, respectively.