Dynamic accumulation of plasmacytoid dendritic cells in lymph nodes is regulated by interferon-beta.
Plasmacytoid dendritic cells (pDCs) represent a major cellular component of our front-line defense against viruses because of their capacity to rapidly secrete type I interferon (IFN)-alpha and -beta after infection. Constant immunosurveillance of the host requires that lymphocytes traffic through lymph nodes (LNs) to sample antigen, yet little is known about the dynamics of pDC accumulation within the secondary lymphoid organs. Here we show that pDCs readily accumulate within the secondary lymphoid organs of mice after virus infection. Interestingly, retention of pDC within LNs is enhanced in the presence of the sphingoshine-1-phosphate receptor agonist FTY720 in a manner similar to that observed for B and T lymphocytes. Ex vivo comparison of mouse pDCs with lymphocytes revealed that pDCs express sphingoshine-1-phosphate 4 and also constitutively express CD69, which is further up-regulated upon virus infection. In IFN-beta(-/-) mice, accumulation of pDC and lymphocytes within LNs is reduced both during viral infection and under steady state conditions, and these defects can be reversed by adding recombinant IFN-beta in vivo. These data suggest that pDC and lymphocytes use similar mechanisms for retention within LNs and that these processes are influenced by IFN-beta even in the absence of viral infection.
Gao
Yunfei
Y
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Majchrzak-Kita
Beata
B
Fish
Eleanor N
EN
Gommerman
Jennifer L
JL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D037181:Lectins, C-Type; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016898:Interferon-alpha; D016899:Interferon-beta; D037181:Lectins, C-Type; D011994:Recombinant Proteins; D000099192:CD69 Antigens