Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected with Leishmania amazonensis
Interactions with apoptotic but not with necrotic neutrophils increase parasite burden in human macrophages infected with Leishmania amazonensis
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DOI：
10.1189/jlb.0108018
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发表时间：
2008-08-01
影响因子：
5.5
通讯作者：
Brodskyn, Claudia I.
中科院分区：
文献类型：
--
作者：
Afonso, Lilian;Borges, Valeria M.;Brodskyn, Claudia I.
中性粒细胞参与了大多数病原体反应的初始步骤。在本研究中，我们评估了凋亡与坏死的人类中性粒细胞的相互作用对巨噬细胞感染亚马逊利什曼原虫的影响。利什曼原虫感染的巨噬细胞吞噬凋亡但不能存活的中性粒细胞，通过依赖于TGF-β 1和PGE的机制导致寄生虫负荷增加（2）。相反，感染的巨噬细胞对坏死的中性粒细胞的摄取诱导了L。亚马逊河。杀利什曼菌活性依赖于TNF-α和嗜酸性弹性蛋白酶。一氧化氮不参与杀死寄生虫，但坏死的中性粒细胞与受感染的巨噬细胞的相互作用导致高超氧化物的产生，过氧化氢酶，活性氧中间产物的抑制剂逆转的过程。利什曼原虫感染后的初始事件涉及与中性粒细胞的相互作用;我们证明，这些细胞在凋亡或坏死阶段的吞噬作用可以影响感染的结果，从而驱动寄生虫的生存或破坏。
Neutrophils are involved in the initial steps of most responses to pathogens. In the present study, we evaluated the effects of the interaction of apoptotic vs. necrotic human neutrophils on macrophage infection by Leishmania amazonensis. Phagocytosis of apoptotic, but not viable, neutrophils by Leishmania-infected macrophages led to an increase in parasite burden via a mechanism dependent on TGF-beta 1 and PGE(2). Conversely, infected macrophages' uptake of necrotic neutrophils induced killing of L. amazonensis. Leishmanicidal activity was dependent on TNF-alpha and neutrophilic elastase. Nitric oxide was not involved in the killing of parasites, but the interaction of necrotic neutrophils with infected macrophages resulted in high superoxide production, a process reversed by catalase, an inhibitor of reactive oxygen intermediate production. Initial events after Leishmania infection involve interactions with neutrophils; we demonstrate that phagocytosis of these cells in an apoptotic or necrotic stage can influence the outcome of infection, driving either parasite survival or destruction.