Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning.
Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning.
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DOI：
10.1038/s41598-020-79703-2
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发表时间：
2021-01-08
影响因子：
4.6
通讯作者：
Akkoyunlu M
中科院分区：
文献类型：
--
作者：
Parra M;Yang J;Weitner M;Akkoyunlu M
我们建立了一个新生小鼠约氏疟原虫感染模型，用于研究早期疟疾。令人惊讶的是，与成年小鼠相比，约氏疟原虫攻击的NB小鼠中寄生虫血症的发作延迟，并且与断奶日期一致，此时断奶仔猪从母乳转变为正常食物饮食。此外，与成年小鼠相比，寄生虫血症消退更晚（攻毒后48天vs 20天），断奶仔猪的寄生虫血症峰值是其两倍。同时，与成年小鼠相比，断奶小鼠的生发中心反应延迟并减弱。母乳中缺乏对氨基苯甲酸（PABA），这是疟原虫从头合成叶酸所必需的。这表明PABA缺乏的母乳提供的保护可能发挥作用，断奶后喂食PABA缺乏饮食的小鼠继续控制寄生虫血症。尽管减少了寄生虫血症，但这些小鼠产生了稳健的T滤泡辅助细胞（Tfh）应答，并受到保护免于第二次约氏疟原虫攻击。NB疟疾模型提供了对人类婴儿疟疾表现的机制性见解，其中仅基于母乳喂养的饮食减少了婴儿中严重疟疾的发病率。NB小鼠实验还支持进一步研究，以调查饮食PABA限制在婴儿重症疟疾管理中的作用。
We developed a newborn (NB) mouse Plasmodium yoelii NL infection model to study malaria in early age. Surprisingly, the onset of parasitemia in P. yoelii challenged NB mice was delayed compared to adults and coincided with the weaning date when weanlings switched from maternal milk to normal chow diet. Also, compared to adult mice, parasitemia resolved much later (48 days vs 20 days post challenge) and the peak parasitemia was twice as high in weanlings. Concurrently, weanlings’ germinal center reaction was delayed and diminished compared to adult mice. Maternal milk is deficient in para-aminobenzoic acid (PABA), which is required for de novo folate synthesis by Plasmodium. Suggesting a possible role for the protection afforded by PABA-deficient maternal milk, mice fed with a PABA-deficient diet after the weaning continued to control parasitemia. Despite the reduced parasitemia, these mice developed robust T follicular helper (Tfh) responses and were protected from a second P. yoelii challenge. The NB malaria model provides mechanistic insight into the human infant malaria manifestations where a diet solely based on breast-feeding reduces the incidence of severe malaria in infants. NB mice experiments also support further studies to investigate dietary PABA restriction in the management of severe malaria in infants.
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影响因子：
15.8
作者：
Chen I;Clarke SE;Gosling R;Hamainza B;Killeen G;Magill A;O'Meara W;Price RN;Riley EM
通讯作者：
Riley EM
影响因子：
3
作者：
D'Alessandro U;Ubben D;Hamed K;Ceesay SJ;Okebe J;Taal M;Lama EK;Keita M;Koivogui L;Nahum A;Bojang K;Sonko AA;Lalya HF;Brabin B
通讯作者：
Brabin B
影响因子：
105.7
作者：
HAWKING, F
通讯作者：
HAWKING, F
影响因子：
--
作者：
HAWKING, F
通讯作者：
HAWKING, F
影响因子：
8.8
作者：
Matz, Joachim Michael;Watanabe, Mutsumi;Matuschewski, Kai
通讯作者：
Matuschewski, Kai