Stephen Tukwasibwe, Savannah Nicole Lewis, Yoweri Taremwa, Kattria van der Ploeg, Kathleen D Press, Maureen Ty, Felistas Namirimu Nankya, Kenneth Musinguzi, Evelyn Nansubuga, Florian Bach, Martin Chamai, Martin Okitwi, Gerald Tumusiime, Annettee Nakimuli, Francesco Colucci, Moses R Kamya, Joaniter I Nankabirwa, Emmanuel Arinaitwe, Bryan Greenhouse, Grant Dorsey, Philip J Rosenthal, Isaac Ssewanyana, Prasanna Jagannathan
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Cellular phenotypes from malaria-exposed donors reflected this specialisation for ADCC, with a compartment-wide downregulation of the Fc receptor γ-chain and enrichment of highly differentiated CD56<sup>dim</sup> and CD56<sup>neg</sup> populations. NK cell degranulation was enhanced in response to opsonised <i>P. falciparum</i> schizonts cultured in sickle cell heterozygous erythrocytes relative to wild-type erythrocytes, and when using opsonising plasma collected from donors living in a high transmission area compared to a lower transmission area despite similar levels of 3D7 schizont-specific IgG levels. However, degranulation was lowered in response to opsonised field isolate <i>P. falciparum</i> schizonts isolated from clinical malaria infections, compared to the 3D7 laboratory strain typically used in these assays.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>This work highlights important host and parasite factors that contribute to ADCC efficacy that should be considered in the design of ADCC assays.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 11","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70005","citationCount":"0","resultStr":"{\"title\":\"Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission\",\"authors\":\"Stephen Tukwasibwe, Savannah Nicole Lewis, Yoweri Taremwa, Kattria van der Ploeg, Kathleen D Press, Maureen Ty, Felistas Namirimu Nankya, Kenneth Musinguzi, Evelyn Nansubuga, Florian Bach, Martin Chamai, Martin Okitwi, Gerald Tumusiime, Annettee Nakimuli, Francesco Colucci, Moses R Kamya, Joaniter I Nankabirwa, Emmanuel Arinaitwe, Bryan Greenhouse, Grant Dorsey, Philip J Rosenthal, Isaac Ssewanyana, Prasanna Jagannathan\",\"doi\":\"10.1002/cti2.70005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>Natural killer (NK) cells make important contributions to anti-malarial immunity through antibody-dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We compared the functions and phenotypes of NK cells from malaria-exposed and malaria-naive donors, and then varied the erythrocyte genetic background, <i>Plasmodium falciparum</i> strain and opsonising plasma used in ADCC to observe their impacts on NK cell degranulation as measured by CD107a mobilisation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Natural killer cells from malaria-exposed adult Ugandan donors had enhanced ADCC, but an impaired pro-inflammatory response to cytokine stimulation, compared to NK cells obtained from malaria-naive adult North American donors. 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引用次数: 0
摘要
目的 自然杀伤（NK）细胞通过抗体依赖性细胞毒性（ADCC）对抗疟免疫做出了重要贡献，但这一途径的不同成分在促进 NK 细胞活化方面的作用仍不清楚。 方法 我们比较了来自疟疾暴露供体和疟疾免疫供体的 NK 细胞的功能和表型，然后改变了 ADCC 中使用的红细胞遗传背景、恶性疟原虫菌株和疏松血浆，以观察它们对 NK 细胞脱颗粒的影响（通过 CD107a 动员测量）。 结果 与来自对疟疾免疫的北美成年供体的 NK 细胞相比，来自疟疾暴露的乌干达成年供体的自然杀伤细胞的 ADCC 增强，但对细胞因子刺激的促炎反应减弱。疟疾暴露供体的细胞表型反映了这种ADCC特化，Fc受体γ-链在整个区段范围内下调，高度分化的CD56dim和CD56neg种群富集。与野生型红细胞相比，在镰状细胞杂合子红细胞中培养的恶性疟原虫裂殖体的疏松化过程中，NK细胞的脱颗粒反应增强；尽管3D7裂殖体特异性IgG水平相似，但与低传播地区相比，当使用从高传播地区捐献者处收集的疏松化血浆时，NK细胞的脱颗粒反应也增强。然而，与这些试验中通常使用的 3D7 实验室菌株相比，对从临床疟疾感染中分离出来的野外分离的恶性疟原虫裂殖体的去颗粒化反应较低。 结论 这项工作强调了促进 ADCC 效能的重要宿主和寄生虫因素，在设计 ADCC 试验时应考虑到这些因素。
Natural killer cell antibody-dependent cellular cytotoxicity to Plasmodium falciparum is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission
Objectives
Natural killer (NK) cells make important contributions to anti-malarial immunity through antibody-dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear.
Methods
We compared the functions and phenotypes of NK cells from malaria-exposed and malaria-naive donors, and then varied the erythrocyte genetic background, Plasmodium falciparum strain and opsonising plasma used in ADCC to observe their impacts on NK cell degranulation as measured by CD107a mobilisation.
Results
Natural killer cells from malaria-exposed adult Ugandan donors had enhanced ADCC, but an impaired pro-inflammatory response to cytokine stimulation, compared to NK cells obtained from malaria-naive adult North American donors. Cellular phenotypes from malaria-exposed donors reflected this specialisation for ADCC, with a compartment-wide downregulation of the Fc receptor γ-chain and enrichment of highly differentiated CD56dim and CD56neg populations. NK cell degranulation was enhanced in response to opsonised P. falciparum schizonts cultured in sickle cell heterozygous erythrocytes relative to wild-type erythrocytes, and when using opsonising plasma collected from donors living in a high transmission area compared to a lower transmission area despite similar levels of 3D7 schizont-specific IgG levels. However, degranulation was lowered in response to opsonised field isolate P. falciparum schizonts isolated from clinical malaria infections, compared to the 3D7 laboratory strain typically used in these assays.
Conclusion
This work highlights important host and parasite factors that contribute to ADCC efficacy that should be considered in the design of ADCC assays.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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