Dalod Marc, Hamilton Tanya, Salomon Rachelle, Salazar-Mather Thais P, Henry Stanley C, Hamilton John D, Biron Christine A
Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Box G-B629, Brown University, Providence, RI 02912, USA.
J Exp Med. 2003 Apr 7;197(7):885-98. doi: 10.1084/jem.20021522.
Differentiation of dendritic cells (DCs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. Plasmacytoid dendritic cells (PDCs) are major producers of interferon (IFN)-alpha/beta in response to many viruses. Here, the functions of these and other splenic DC subsets are further analyzed after in vivo infection with murine cytomegalovirus (MCMV). Viral challenge induced PDC maturation, their production of high levels of innate cytokines, and their ability to activate natural killer (NK) cells. The conditions also licensed PDCs to efficiently activate CD8 T cells in vitro. Non-plasmacytoid DCs induced T lymphocyte activation in vitro. As MCMV preferentially infected CD8alpha+ DCs, however, restricted access to antigens may limit plasmacytoid and CD11b+ DC contribution to CD8 T cell activation. IFN-alpha/beta regulated multiple DC responses, limiting viral replication in all DC and IL-12 production especially in the CD11b+ subset but promoting PDC accumulation and CD8alpha+ DC maturation. Thus, during defense against a viral infection, PDCs appear specialized for initiation of innate, and as a result of their production of IFN-alpha/beta, regulate other DCs for induction of adaptive immunity. Therefore, they may orchestrate the DC subsets to shape endogenous immune responses to viruses.
树突状细胞（DCs）分化为特定亚群可能会影响先天性和适应性免疫反应，但对于感染期间这一过程如何发生却知之甚少。浆细胞样树突状细胞（PDCs）是对多种病毒产生干扰素（IFN）-α/β的主要细胞。在此，在用鼠巨细胞病毒（MCMV）进行体内感染后，对这些以及其他脾脏DC亚群的功能进行了进一步分析。病毒攻击诱导了PDC的成熟、其高水平先天性细胞因子的产生以及激活自然杀伤（NK）细胞的能力。这些条件还使PDC能够在体外有效激活CD8 T细胞。非浆细胞样DC在体外诱导T淋巴细胞活化。然而，由于MCMV优先感染CD8α+ DC，抗原获取受限可能会限制浆细胞样和CD11b+ DC对CD8 T细胞活化的作用。IFN-α/β调节多种DC反应，限制所有DC中的病毒复制以及IL-12的产生，尤其是在CD11b+亚群中，但促进PDC的积累和CD8α+ DC的成熟。因此，在抵御病毒感染期间，PDC似乎专门用于启动先天性免疫，并且由于其产生IFN-α/β，调节其他DC以诱导适应性免疫。因此，它们可能协调DC亚群以塑造针对病毒的内源性免疫反应。
