IL-12 producing monocytes and IFN-γ and TNF-α producing T-lymphocytes are increased in placentas infected by Plasmodium falciparum
IL-12 producing monocytes and IFN-γ and TNF-α producing T-lymphocytes are increased in placentas infected by Plasmodium falciparum
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DOI：
10.1016/j.jri.2006.10.001
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Decloron, Philippe
中科院分区：
文献类型：
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作者：
Diouf, Ibrahima;Fievet, Nadine;Decloron, Philippe
胎盘恶性疟原虫隔离与免疫功能失调有关。通过IFN-γ和TNF-α的胎盘炎症反应与功能损伤有关。然而，在胎盘感染期间需要它们来控制无性阶段的寄生虫。为了检验与疟疾相关的胎盘免疫调节对单核细胞和淋巴细胞中细胞因子分泌的不同干扰这一假设，我们测定了分泌IFN-γ、TNF-α、IL-10和IL-12的单核细胞和/或淋巴细胞的比例。比较了17名感染恶性疟原虫的塞内加尔妇女和12名未感染恶性疟原虫的塞内加尔妇女的CD 3/CD 4（+）; CD 3/CD 8（+）细胞因子的产生。用佛波酯/离子霉素（PMA/iono）、脂多糖（LPS）或恶性疟原虫感染的红细胞（IE）培养后，检测淋巴细胞（IFN-γ、TNF-α）和单核细胞（IL-10、IL-12、TNF-α）中细胞因子的表达。作为对IE的反应，CD 4（+）和CD 8（+）T细胞在两个隔室中以相似的速率产生IFN-γ和TNF-α。对PMA/iono的反应，产生IFN-γ和TNF-α的CD 4（+）和CD 8（+）T细胞的频率在两个隔室中相似，但在恶性疟原虫感染的胎盘中增加。在LPS或IE的刺激下，感染者分泌IL-12的单核细胞增多，而分泌TNF-α的单核细胞减少，感染者单核细胞IL-12反应不受影响。IL- 12是诱导T细胞中IFN-γ的重要因子。因此，IL-12和IFN-α应答可能协同地允许胎盘疟疾中的保护性免疫应答。在恶性疟原虫感染的胎盘中，CD 4（+）和CD 8（+）T细胞产生的TNF-α上调，表明T细胞积极参与炎症反应。(C)2006爱思唯尔爱尔兰有限公司保留所有权利。
Placental Plasmodium falciparum sequestration is associated with dysregulated immune function. Placental inflammatory responses via IFN-gamma and TNF-alpha are implicated in functional damage. However, they are needed during placental infection to control asexual stage parasites. To test the hypothesis that placental immunomodulation associated with malaria disturbs cytokine secretion differently in monocytes and lymphocytes, we have determined the proportion of monocytes and/or lymphocytes secreting IFN-gamma, TNF-alpha, IL-10 and IL-12.Intervillous and peripheral blood monocyte (CD14(+)) and lymphocyte (CD3/CD4(+); CD3/CD8(+)) cytokine production was compared between 17 P. falciparum-infected and 12 non-infected Senegalese women. After culture with phorbolmyristate acetate/ionomycin (PMA/iono), lipopolysaccharide (LPS) or P. falciparum-infected erythrocytes (IE), the intracellular expression of cytokines in lymphocytes (IFN-gamma, TNF-alpha) and monocytes (IL-10, IL-12, TNF-alpha), was detected. In response to IE, CD4(+) and CD8(+) T-cells produced IFN-gamma and TNF-alpha at similar rates in both compartments. In response to PMA/iono, the frequencies of CD4(+) and CD8(+) T-cells producing IFN-gamma and TNF-alpha were similar in both compartments, but increased in P. falciparum-infected placentas. In response to LPS or IE, IL-12 secreting monocytes were increased in infected women, while the frequency of TNF-alpha secreting monocytes was decreased compared to that in non-infected placenta.The monocyte IL-12 response is not impaired in infected women. IL- 12 is an important factor for inducing IFN-gamma in T-cells. Thus, 1L-12 and IFN-alpha responses may synergistically allow a protective immune response in placental malaria. TNF-alpha production by CD4(+) and CD8(+) T-cells, is up-regulated in P falciparum-infected placentas, suggesting that T-cells actively participate to inflammatory responses. (C) 2006 Elsevier Ireland Ltd. All rights reserved.