Dendritic Cell and NK Cell Reciprocal Cross Talk Promotes Gamma Interferon-Dependent Immunity to Blood-Stage Plasmodium chabaudi AS Infection in Mice
Dendritic Cell and NK Cell Reciprocal Cross Talk Promotes Gamma Interferon-Dependent Immunity to Blood-Stage Plasmodium chabaudi AS Infection in Mice
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DOI：
10.1128/iai.00994-08
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发表时间：
2009-02-01
影响因子：
3.1
通讯作者：
Stevenson, Mary M.
中科院分区：
文献类型：
--
作者：
Ing, Rebecca;Stevenson, Mary M.
树突状细胞（Dendritic cells，DC）是一种重要的辅助细胞，在恶性疟原虫感染的红细胞（Plasmodium falciparum infected red blood cells，iRBC）体外刺激NK细胞产生γ-干扰素（IFN-γ）。我们研究了DCs和NK细胞相互激活导致Th 1型先天性和适应性免疫对夏氏疟原虫AS感染的要求。在感染的第一周，抗性野生型（WT）C57 BL/6小鼠中脾脏CD 11 c（+）DC对iRBC的摄取与白细胞介素15（-/-）（IL-15（-/-））和IL-12 p40（-/-）小鼠相似，这两种小鼠在夏氏疟原虫AS感染的严重程度上不同。来自感染IL-15（-/-）小鼠的DC表达共刺激分子，产生IL-12，并在体外与WT DC一样有效地促进WT NK细胞分泌IFN-γ。相反，来自感染IL-12 p40（-/-）小鼠的DC表现出成熟和细胞因子产生的改变，并且不能诱导NK细胞IFN-γ产生。DC和NK细胞的共培养证明DC介导的NK细胞活化需要IL-12，并且在较小程度上需要IL-2，以及细胞-细胞接触。反过来，来自感染的WT小鼠的NK细胞增强了DC成熟、IL-12产生以及CD 4（+）T细胞增殖和IFN-γ分泌的引发。NK细胞耗竭的感染WT小鼠表现出寄生虫血症增加，DC成熟和DC诱导的CD 4（+）Th 1细胞引发受损。这些发现表明DC-NK细胞相互串扰对于控制和快速解决夏氏疟原虫AS感染至关重要，并提供了这种相互作用在IFN-γ依赖性疟疾免疫中的重要性的体内证据。
Dendritic cells (DCs) are important accessory cells for promoting NK cell gamma interferon (IFN-gamma) production in vitro in response to Plasmodium falciparum-infected red blood cells (iRBC). We investigated the requirements for reciprocal activation of DCs and NK cells leading to Th1-type innate and adaptive immunity to P. chabaudi AS infection. During the first week of infection, the uptake of iRBC by splenic CD11c(+) DCs in resistant wild-type (WT) C57BL/6 mice was similar to that in interleukin 15(-/-) (IL-15(-/-)) and IL-12p40(-/-) mice, which differ in the severity of P. chabaudi AS infection. DCs from infected IL-15(-/-) mice expressed costimulatory molecules, produced IL-12, and promoted IFN-gamma secretion by WT NK cells in vitro as efficiently as WT DCs. In contrast, DCs from infected IL-12p40(-/-) mice exhibited alterations in maturation and cytokine production and were unable to induce NK cell IFN-gamma production. Coculture of DCs and NK cells demonstrated that DC-mediated NK cell activation required IL-12 and, to a lesser extent, IL-2, as well as cell-cell contact. In turn, NK cells from infected WT mice enhanced DC maturation, IL-12 production, and priming of CD4(+) T-cell proliferation and IFN-gamma secretion. Infected WT mice depleted of NK cells, which exhibit increased parasitemia, had impaired DC maturation and DC-induced CD4(+) Th1 cell priming. These findings indicate that DC-NK cell reciprocal cross talk is critical for control and rapid resolution of P. chabaudi AS infection and provide in vivo evidence for the importance of this interaction in IFN-gamma-dependent immunity to malaria.