Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production of soluble factors reducing brain microvascular barrier function.
Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production of soluble factors reducing brain microvascular barrier function.
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DOI：
10.1371/journal.pone.0285323
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Craig, Alister G.
中科院分区：
文献类型：
--
作者：
Storm, Janet;Camarda, Grazia N.;Haley, Michael J. G.;Brough, David;Couper, Kevin N.;Craig, Alister G.
单核细胞在恶性疟原虫感染的血液阶段有助于促炎免疫反应，但它们在疟疾病理学中的确切作用尚不清楚。除了吞噬作用外，单核细胞还可以被恶性疟原虫感染的红细胞 (IE) 的产物激活，其中一个激活途径可能是包含 NLR 家族吡啶结构域 3 (NLRP3) 炎性体，这是一种多蛋白复合物，可导致白细胞介素 (IL)-1β 的产生。在脑型疟疾病例中，单核细胞在脑微血管中的 IE 隔离位点积聚，局部产生的 IL-1β 或其他分泌分子可能导致血脑屏障渗漏。为了在体外模型中研究 IE 对脑微血管内单核细胞的激活，我们将 IT4var14 IE 和单核细胞系 THP-1 共培养 24 小时，并通过实时跨内皮电阻测量，确定生成的可溶性分子是否影响人脑微血管内皮细胞的屏障功能。共培养后产生的培养基不影响内皮屏障功能，并且在通过向共培养物中添加黄嘌呤氧化酶诱导氧化应激后同样没有测量到影响。虽然 IL-1β 确实降低了屏障功能，但在共培养物中几乎不产生任何 IL-1β，这表明在该共培养模型中 IE 缺乏或不完全激活 THP-1。
Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.
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DOI：
10.1128/cvi.00533-16
发表时间：
2017-04
期刊：
Clinical and vaccine immunology : CVI
影响因子：
--
作者：
Mandala WL;Msefula CL;Gondwe EN;Drayson MT;Molyneux ME;MacLennan CA
通讯作者：
MacLennan CA
影响因子：
10.6
作者：
Downs KP;Nguyen H;Dorfleutner A;Stehlik C
通讯作者：
Stehlik C
影响因子：
4.6
作者：
Aljayyoussi G;Jenkins VA;Sharma R;Ardrey A;Donnellan S;Ward SA;Biagini GA
通讯作者：
Biagini GA
影响因子：
7.3
作者：
Gritsenko A;Yu S;Martin-Sanchez F;Diaz-Del-Olmo I;Nichols EM;Davis DM;Brough D;Lopez-Castejon G
通讯作者：
Lopez-Castejon G
影响因子：
3.7
作者：
Khaw, Loke Tim;Ball, Helen J.;Hunt, Nicholas H.
通讯作者：
Hunt, Nicholas H.