Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response
Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response
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DOI：
10.1002/eji.200636771
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Sasiain, Maria
中科院分区：
文献类型：
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作者：
Aleman, Mercedes;de la Barrera, Silvia;Sasiain, Maria
多形核中性粒细胞（PNIN）通过与未成熟树突状细胞（iDC）的相互作用调节适应性免疫应答，而自发凋亡中性粒细胞（PMNapo）可能对DC功能具有抑制作用。我们研究了PMNapo在DC成熟中的作用以及结核分枝杆菌（Mtb）诱导的PMNapo在分枝杆菌抗原交叉呈递中的作用。我们证明，Mtb触发iDC的成熟，而它是由PMNapo的存在下，废除Mtb诱导的共刺激分子和HLA II类分子的表达，减少DC的IL-12和IFN-γ的释放和部分抑制Mtb驱动的淋巴细胞增殖受损。在已经Mtb成熟的DC中没有观察到这种抑制作用，并且它涉及DC和PMNapo之间的直接相互作用，因为来自PMNapo培养物的上清液没有显示这种作用。虽然PMNapo不改变Mtb/DC-SIGN相互作用，但它们影响导致DC成熟的细胞内信号，而不需要它们进入DC。iDC对Mtb诱导的PMNapo的吞噬作用导致淋巴细胞增殖，其通过阻断iDC上的CD 36而不是DC-SIGN而显著降低。因此，Mtb抗原的交叉呈递正在发生。我们的研究结果表明，炎症环境受到非感染和结核分枝杆菌诱导的PMNapo之间的良好平衡：非感染的PMNapo限制炎症和结核分枝杆菌诱导的PMNapo产生特定的免疫活性。
Polymorphonuclear neutrophils (PNIN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-gamma release by DC and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DC, and it involves a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction, they affect the intracellular signals leading to DC maturation without requiring their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to lymphoproliferation, which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting inflammation and Mtb-induced PMNapo generating a specific immune activity.