Nmnat3 deficiency in hemolytic anemia exacerbates malaria infection
Nmnat3 deficiency in hemolytic anemia exacerbates malaria infection
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溶血性贫血中的 Nmnat3 缺乏会加剧疟疾感染
DOI：
10.1016/j.bbrc.2022.11.003
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发表时间：
2022
影响因子：
3.1
通讯作者：
Nakagawa Takashi
中科院分区：
文献类型：
--
作者：
Mahmood Arshad;Yaku Keisuke;Hikosaka Keisuke;Gulshan Maryam;Inoue Shin-ichi;Kobayashi Fumie;Nakagawa Takashi
疟疾是一种由疟原虫引起的传染病，死亡率很高，特别是在非洲和东南亚国家的儿童中。建议溶血性贫血患者采取预防疟疾感染的措施。烟酰胺腺嘌呤二核苷酸（NAD+）是一种重要的辅因子，与许多生物过程有关，维持所有生物体内的稳态。在先前的研究中，我们已经证明，缺乏烟酰胺单核苷酸腺苷酰转移酶3（Nmnat 3），一种催化NAD+合成的酶，会导致溶血性贫血，伴随着红细胞中NAD+水平的急剧下降。众所周知，溶血性贫血与降低疟疾感染风险有关。在本研究中，我们调查了由Nmnat3缺乏引起的溶血性贫血是否有益于对抗疟疾感染。我们发现，Nmnat3缺乏加剧了疟疾感染，随后导致死亡。此外，我们证明了疟疾感染的Nmnat3红细胞中的NAD+水平显著增加，糖酵解流量大大增强，以支持疟疾寄生虫的快速生长。我们的研究结果表明，由Nmnat3缺失引起的溶血性贫血是有害的，而不是对疟疾的保护。
Malaria is an infectious disease caused byPlasmodiumparasites and has high mortality rates, especially among children in African and Southeast Asian countries. Patients with hemolytic anemia are suggested to adapt protective measures against malarial infection. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor associated with numerous biological processes that maintain homeostasis in all living organisms. In a previous study, we had demonstrated that the deficiency of nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3), an enzyme catalyzing NAD+synthesis, causes hemolytic anemia accompanied by a drastic decline in the NAD+levels in the erythrocytes. It is well known that hemolytic anemia is linked to a reduced risk of malarial infections. In the present study, we investigated whether hemolytic anemia caused by Nmnat3 deficiency is beneficial against malarial infections. We found that Nmnat3 deficiency exacerbated malarial infection and subsequently caused death. Moreover, we demonstrated that the NAD+levels in malaria-infected Nmnat3 red blood cells significantly increased and the glycolytic flow was largely enhanced to support the rapid growth of malarial parasites. Our results revealed that hemolytic anemia induced by the deletion of Nmnat3 was harmful rather than protective against malaria.