Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses.
T helper type 1 (T(H)1)-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(+)CD11b(hi)Gr-1(+) inflammatory DCs, which produced abundant interleukin 12p70 and potently stimulated T(H)1 responses. This monocyte extravasation required the chemokine receptor CCR2 but not the chemokine CCL2 or receptor CCR7. Thus, the accumulation of inflammatory DCs and T(H)1 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 T(H)1 immune responses.
Nakano
Hideki
H
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Lin
Kaifeng Lisa
KL
Yanagita
Manabu
M
Charbonneau
Chantal
C
Cook
Donald N
DN
Kakiuchi
Terutaka
T
Gunn
Michael D
MD
D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D018925:Chemokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009976:Orthomyxoviridae Infections / Q000276:immunology; D054390:Receptors, CCR2 / Q000235:genetics; D019707:Receptors, Chemokine / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine