Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities.
The migration capability of dendritic cells (DCs) is regulated by their response to factors, namely chemokines, that characterize maturation stage and shape their functional activities. This study examines the morphology, expression of chemokines/chemokine receptors, and migration properties of DCs generated after treatment of monocytes with type I interferon (IFN) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (IFN-DCs). IFN-DCs showed phenotypical and morphologic features undetectable in DCs generated in the presence of interleukin 4 (IL-4) and GM-CSF, such as expression of CD83 and CD25 and the presence of CD44+, highly polarized, thin, and long dendrites. IFN-DCs markedly migrated in response to beta-chemokines (especially MIP-1beta) and expressed the Th-1 chemokine IP-10. Notably, IFN-DCs showed an up-regulation of CCR7 as well as of its natural ligand MIP-3beta, characteristics typical of mature DCs. Of interest, IFN-DCs exhibited a marked chemotactic response to MIP-3beta in vitro and strong migratory behavior in severe combined immunodeficient (SCID) mice. In SCID mice reconstituted with human peripheral blood leukocytes, IFN-DCs induced a potent primary human antibody response and IFN-gamma production, indicative of a Th-1 immune response. These results define the highly specialized maturation state of IFN-DCs and point out the existence of a "natural alliance" between type I IFN and monocyte/DC development, instrumental for ensuring an efficient connection between innate and adaptive immunity.
Parlato
S
S
Laboratory of Virology, Laboratory of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Santini
S M
SM
Lapenta
C
C
Di Pucchio
T
T
Logozzi
M
M
Spada
M
M
Giammarioli
A M
AM
Malorni
W
W
Fais
S
S
Belardelli
F
F
D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis; D017951:Antigen Presentation; D002465:Cell Movement; D022081:Cell Surface Extensions / Q000648:ultrastructure; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007114:Immunization; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000166:cytology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; C515460:CCL19 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D016898:Interferon-alpha; D008222:Lymphokines; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor