Malleret Benoît, Manéglier Benjamin, Karlsson Ingrid, Lebon Pierre, Nascimbeni Michelina, Perié Leïla, Brochard Patricia, Delache Benoît, Calvo Julien, Andrieu Thibault, Spreux-Varoquaux Odile, Hosmalin Anne, Le Grand Roger, Vaslin Bruno
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
Blood. 2008 Dec 1;112(12):4598-608. doi: 10.1182/blood-2008-06-162651. Epub 2008 Sep 11.
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.
浆细胞样树突状细胞（pDC）是抗原呈递细胞，可在病原体刺激下分化为产生I型干扰素（IFN-I）的细胞。它们在人类免疫缺陷病毒（HIV）发病机制中的作用尚待明确。我们分析了18只猕猴感染猿猴免疫缺陷病毒（SIV）急性期极早期时，pDC与固有免疫和适应性免疫相关的动态变化。血液中的pDC数量减少，外周淋巴结中的pDC数量增加，这与pDC早期募集至二级淋巴组织一致。这些变化与病毒血症的动力学和强度相关，并与血浆IFN-I峰值相关。IFN-I和病毒血症与免疫抑制相关酶吲哚胺-2,3-双加氧酶（IDO）和FoxP3(+)CD8(+) T细胞的功能活性呈正相关，而这两者均与SIV特异性T细胞增殖和CD4(+) T细胞活化呈负相关。这些数据表明，在SIV/HIV初次感染急性期，pDC和IFN-I在塑造针对抑制性途径的固有免疫和适应性免疫中起关键作用。
