Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning

Abstract 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 norma...

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Autores principales:	Marcela Parra, Jiyeon Yang, Megan Weitner, Mustafa Akkoyunlu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12379a0cd69945b4bee2c582845f2428
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spelling	oai:doaj.org-article:12379a0cd69945b4bee2c582845f24282021-12-02T11:45:53ZNeonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning10.1038/s41598-020-79703-22045-2322https://doaj.org/article/12379a0cd69945b4bee2c582845f24282021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79703-2https://doaj.org/toc/2045-2322Abstract 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.Marcela ParraJiyeon YangMegan WeitnerMustafa AkkoyunluNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marcela Parra Jiyeon Yang Megan Weitner Mustafa Akkoyunlu Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
description	Abstract 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.
format	article
author	Marcela Parra Jiyeon Yang Megan Weitner Mustafa Akkoyunlu
author_facet	Marcela Parra Jiyeon Yang Megan Weitner Mustafa Akkoyunlu
author_sort	Marcela Parra
title	Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
title_short	Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
title_full	Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
title_fullStr	Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
title_full_unstemmed	Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
title_sort	neonatal mice resist plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/12379a0cd69945b4bee2c582845f2428
work_keys_str_mv	AT marcelaparra neonatalmiceresistplasmodiumyoeliiinfectionuntilexposedtoparaaminobenzoicacidcontainingdietafterweaning AT jiyeonyang neonatalmiceresistplasmodiumyoeliiinfectionuntilexposedtoparaaminobenzoicacidcontainingdietafterweaning AT meganweitner neonatalmiceresistplasmodiumyoeliiinfectionuntilexposedtoparaaminobenzoicacidcontainingdietafterweaning AT mustafaakkoyunlu neonatalmiceresistplasmodiumyoeliiinfectionuntilexposedtoparaaminobenzoicacidcontainingdietafterweaning
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Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning

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