Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression.
Plasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)-producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immunodeficiency virus (SIV) infection in 18 macaques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in secondary lymphoid tissues. These changes correlated with the kinetic and intensity of viremia and were associated with a peak of plasma IFN-I. IFN-I and viremia were positively correlated with functional activity of the immune suppression associated enzyme indoleamine-2,3-dioxygenase (IDO) and FoxP3(+)CD8(+) T cells, which both negatively correlated with SIV-specific T-cell proliferation and CD4(+) T-cell activation. These data suggest that pDCs and IFN-I play a key role in shaping innate and adaptive immunity toward suppressive pathways during the acute phase of SIV/HIV primary infection.
Malleret
Benoît
B
Division of Immuno-Virology SIV, Commissariat à l'Energie Atomique, Institute of Emerging Diseases and Innovative Therapies IMETI, Fontenay-aux-Roses, Université Paris-Sud, Unité Mixte de Recherche E01, Orsay, France
Manéglier
Benjamin
B
Karlsson
Ingrid
I
Lebon
Pierre
P
Nascimbeni
Michelina
M
Perié
Leïla
L
Brochard
Patricia
P
Delache
Benoît
B
Calvo
Julien
J
Andrieu
Thibault
T
Spreux-Varoquaux
Odile
O
Hosmalin
Anne
A
Le Grand
Roger
R
Vaslin
Bruno
B
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D007108:Immune Tolerance / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007370:Interferon Type I / Q000097:blood*; D020382:Interleukin-18 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I; D020382:Interleukin-18; D053645:Interleukin-2 Receptor alpha Subunit