Abstract
T helper type 1 (TH1)-polarized immune responses, which confer protection against intracellular pathogens, are thought to be initiated by dendritic cells (DCs) that enter lymph nodes from peripheral tissues. Here we found after viral infection or immunization, inflammatory monocytes were recruited into lymph nodes directly from the blood to become CD11c+CD11bhiGr-1+ inflammatory DCs, which produced abundant interleukin 12p70 and potently stimulated TH1 responses. This monocyte extravasation required the chemokine receptor CCR2 but not the chemokine CCL2 or receptor CCR7. Thus, the accumulation of inflammatory DCs and TH1 responses were much lower in Ccr2−/− mice, were preserved in Ccl2−/− mice and were relatively higher in CCL19–CCL21-Ser–deficient plt mutant mice, in which all other lymph node DC types were fewer in number. We conclude that blood-derived inflammatory DCs are important in the development of TH1 immune responses.
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Acknowledgements
We thank K. Nakano for technical assistance, and J. Whitesides, P. McDermott and L. Olive for cell sorting. Supported by the National Institutes of Health (AI047262 and HL085473 to M.D.G.), the Japanese Ministry of Science and Technology (1579054 to H.N., and 14021121 to T.K.), the Duke Human Vaccine Institute (H.N.), the Japan Health Sciences Foundation (KH51052 to T.K.), the Japan Society for the Promotion of Science (10670606, 12670621 to T.K.), the Japan Society for the Promotion of Science for Young Scientists (M.Y.) and the intramural branch of the National Institute of Environmental Health Sciences of the National Institutes of Health.
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H.N. and K.L.L. designed and did most experiments, analyzed and interpreted data and contributed to the writing of the manuscript; M.Y. and C.C. designed and did experiments and analyzed and interpreted data; D.N.C. and T.K. provided supervision and research support; and M.D.G. conceived and supervised the project, provided intellectual and research support, and wrote the manuscript.
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Nakano, H., Lin, K., Yanagita, M. et al. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nat Immunol 10, 394–402 (2009). https://doi.org/10.1038/ni.1707
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DOI: https://doi.org/10.1038/ni.1707
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