CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles

Abstract Synthetic CpG-ODNs can promote antimicrobial immunity in neonatal chicks by enriching immune compartments and activating immune cells. Activated immune cells undergo profound metabolic changes to meet cellular biosynthesis and energy demands and facilitate the signaling processes. We hypoth...

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Autores principales:	Kalhari Bandara Goonewardene, Naama Karu, Khawaja Ashfaque Ahmed, Shelly Popowich, Betty Chow-Lockerbie, Lisanework E. Ayalew, Ruwani Karunarathna, Thushari Gunawardana, Mengying Liu, Suresh K. Tikoo, Marianna Foldvari, Philip Willson, Rupasri Mandal, David S. Wishart, Susantha Gomis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01719c93fa794b979262ca838bb4f452
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spelling	oai:doaj.org-article:01719c93fa794b979262ca838bb4f4522021-12-02T17:39:32ZCpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles10.1038/s41598-021-88386-22045-2322https://doaj.org/article/01719c93fa794b979262ca838bb4f4522021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88386-2https://doaj.org/toc/2045-2322Abstract Synthetic CpG-ODNs can promote antimicrobial immunity in neonatal chicks by enriching immune compartments and activating immune cells. Activated immune cells undergo profound metabolic changes to meet cellular biosynthesis and energy demands and facilitate the signaling processes. We hypothesize that CpG-ODNs induced immune activation can change the host’s metabolic demands in neonatal chicks. Here, we used NMR-based metabolomics to explore the potential of immuno-metabolic interactions in the orchestration of CpG-ODN-induced antimicrobial immunity. We administered CpG-ODNs to day-old broiler chicks via intrapulmonary (IPL) and intramuscular (IM) routes. A negative control group was administered IPL distilled water (DW). In each group (n = 60), chicks (n = 40) were challenged with a lethal dose of Escherichia coli, two days post-CpG-ODN administration. CpG-ODN administered chicks had significantly higher survival (P < 0.05), significantly lower cumulative clinical scores (P < 0.05), and lower bacterial loads (P < 0.05) compared to the DW control group. In parallel experiments, we compared NMR-based serum metabolomic profiles in neonatal chicks (n = 20/group, 24 h post-treatment) treated with IM versus IPL CpG-ODNs or distilled water (DW) control. Serum metabolomics revealed that IM administration of CpG-ODN resulted in a highly significant and consistent decrease in amino acids, purines, betaine, choline, acetate, and a slight decrease in glucose. IPL CpG-ODN treatment resulted in a similar decrease in purines and choline but less extensive decrease in amino acids, a stronger decrease in acetate, and a considerable increase in 2-hydroxybutyrate, 3-hydroxybutyrate, formic acid and a mild increase in TCA cycle intermediates (all P < 0.05 after FDR adjustment). These perturbations in pathways associated with energy production, amino acid metabolism and nucleotide synthesis, most probably reflect increased uptake of nutrients to the cells, to support cell proliferation triggered by the innate immune response. Our study revealed for the first time that CpG-ODNs change the metabolomic landscape to establish antimicrobial immunity in neonatal chicks. The metabolites highlighted in the present study can help future targeted studies to better understand immunometabolic interactions and pinpoint the key molecules or pathways contributing to immunity.Kalhari Bandara GoonewardeneNaama KaruKhawaja Ashfaque AhmedShelly PopowichBetty Chow-LockerbieLisanework E. AyalewRuwani KarunarathnaThushari GunawardanaMengying LiuSuresh K. TikooMarianna FoldvariPhilip WillsonRupasri MandalDavid S. WishartSusantha GomisNature 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 Kalhari Bandara Goonewardene Naama Karu Khawaja Ashfaque Ahmed Shelly Popowich Betty Chow-Lockerbie Lisanework E. Ayalew Ruwani Karunarathna Thushari Gunawardana Mengying Liu Suresh K. Tikoo Marianna Foldvari Philip Willson Rupasri Mandal David S. Wishart Susantha Gomis CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
description	Abstract Synthetic CpG-ODNs can promote antimicrobial immunity in neonatal chicks by enriching immune compartments and activating immune cells. Activated immune cells undergo profound metabolic changes to meet cellular biosynthesis and energy demands and facilitate the signaling processes. We hypothesize that CpG-ODNs induced immune activation can change the host’s metabolic demands in neonatal chicks. Here, we used NMR-based metabolomics to explore the potential of immuno-metabolic interactions in the orchestration of CpG-ODN-induced antimicrobial immunity. We administered CpG-ODNs to day-old broiler chicks via intrapulmonary (IPL) and intramuscular (IM) routes. A negative control group was administered IPL distilled water (DW). In each group (n = 60), chicks (n = 40) were challenged with a lethal dose of Escherichia coli, two days post-CpG-ODN administration. CpG-ODN administered chicks had significantly higher survival (P < 0.05), significantly lower cumulative clinical scores (P < 0.05), and lower bacterial loads (P < 0.05) compared to the DW control group. In parallel experiments, we compared NMR-based serum metabolomic profiles in neonatal chicks (n = 20/group, 24 h post-treatment) treated with IM versus IPL CpG-ODNs or distilled water (DW) control. Serum metabolomics revealed that IM administration of CpG-ODN resulted in a highly significant and consistent decrease in amino acids, purines, betaine, choline, acetate, and a slight decrease in glucose. IPL CpG-ODN treatment resulted in a similar decrease in purines and choline but less extensive decrease in amino acids, a stronger decrease in acetate, and a considerable increase in 2-hydroxybutyrate, 3-hydroxybutyrate, formic acid and a mild increase in TCA cycle intermediates (all P < 0.05 after FDR adjustment). These perturbations in pathways associated with energy production, amino acid metabolism and nucleotide synthesis, most probably reflect increased uptake of nutrients to the cells, to support cell proliferation triggered by the innate immune response. Our study revealed for the first time that CpG-ODNs change the metabolomic landscape to establish antimicrobial immunity in neonatal chicks. The metabolites highlighted in the present study can help future targeted studies to better understand immunometabolic interactions and pinpoint the key molecules or pathways contributing to immunity.
format	article
author	Kalhari Bandara Goonewardene Naama Karu Khawaja Ashfaque Ahmed Shelly Popowich Betty Chow-Lockerbie Lisanework E. Ayalew Ruwani Karunarathna Thushari Gunawardana Mengying Liu Suresh K. Tikoo Marianna Foldvari Philip Willson Rupasri Mandal David S. Wishart Susantha Gomis
author_facet	Kalhari Bandara Goonewardene Naama Karu Khawaja Ashfaque Ahmed Shelly Popowich Betty Chow-Lockerbie Lisanework E. Ayalew Ruwani Karunarathna Thushari Gunawardana Mengying Liu Suresh K. Tikoo Marianna Foldvari Philip Willson Rupasri Mandal David S. Wishart Susantha Gomis
author_sort	Kalhari Bandara Goonewardene
title	CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
title_short	CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
title_full	CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
title_fullStr	CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
title_full_unstemmed	CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
title_sort	cpg-odn induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01719c93fa794b979262ca838bb4f452
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CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles

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