Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets

Preterm infants born with immature organ systems, which can impede normal development, can also be highly sensitive to different biological and/or environmental factors. Animal models could aid in investigating and understanding the effects of different conditions on the health of these immunocompro...

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Autores principales: Splichalova, Alla, Slavikova, Vera, Splichalova, Zdislava, Splichal, Igor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817058/
https://www.ncbi.nlm.nih.gov/pubmed/29491864
http://dx.doi.org/10.3389/fimmu.2018.00220
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author Splichalova, Alla
Slavikova, Vera
Splichalova, Zdislava
Splichal, Igor
author_facet Splichalova, Alla
Slavikova, Vera
Splichalova, Zdislava
Splichal, Igor
author_sort Splichalova, Alla
collection PubMed
description Preterm infants born with immature organ systems, which can impede normal development, can also be highly sensitive to different biological and/or environmental factors. Animal models could aid in investigating and understanding the effects of different conditions on the health of these immunocompromised infants. The epitheliochorial placentation of the pig prevents the prenatal transfer of protective colostral immunoglobulins. Surgical colostrum-deprived piglets are free of maternal immunoglobulins, and the cells that are normally provided via colostrum. We bred preterm germ-free piglets in sterile conditions and compared them with their term counterparts. Enterocyte development and intestinal morphology, tight junction proteins claudin-1 and occludin, pattern-recognizing receptors, adaptor molecules and coreceptors (RAGE, TLR2, TLR4, TLR9, MyD88, TRIF, MD2, and CD14), and inflammasome NLRP3 transcription were all evaluated. The production of inflammatory mediators IFN-α, IL-4, IL-6, IL-8, IL-10, IL-12/23 p40, TNF-α, IFN-γ, and high mobility group box 1 (HMGB1) in the intestine of germ-free piglets was also assessed. In the preterm germ-free piglets, the ileum showed decreased lamina propria cellularity, reduced villous height, and thinner and less distinct stratification – especially muscle layer, in comparison with their term counterparts. Claudin-1 transcription increased in the intestine of the preterm piglets. The transcription levels of pattern-recognizing receptors and adaptor molecules showed ambiguous trends between the groups. The levels of IL-6, IL-8, IL-10, and TNF-α were increased in the preterm ileum numerically (though not significantly), with statistically significant increases in the colon. Additionally, IL-12/23 p40 and IFN-γ were statistically significantly higher in the preterm colon. Both blood plasma and intestinal HMGB1 levels were nonsignificantly higher in the preterm group. We propose that the intestine of the preterm germ-free piglets showed “mild inflammation in sterile conditions.” This model, which establishes preterm, hysterectomy-derived germ-free piglets, without protective maternal immunoglobulins, can be used to study influences of microbiota, nutrition, and therapeutic interventions on the development and health of vulnerable immunocompromised preterm infants.
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spelling pubmed-58170582018-02-28 Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets Splichalova, Alla Slavikova, Vera Splichalova, Zdislava Splichal, Igor Front Immunol Immunology Preterm infants born with immature organ systems, which can impede normal development, can also be highly sensitive to different biological and/or environmental factors. Animal models could aid in investigating and understanding the effects of different conditions on the health of these immunocompromised infants. The epitheliochorial placentation of the pig prevents the prenatal transfer of protective colostral immunoglobulins. Surgical colostrum-deprived piglets are free of maternal immunoglobulins, and the cells that are normally provided via colostrum. We bred preterm germ-free piglets in sterile conditions and compared them with their term counterparts. Enterocyte development and intestinal morphology, tight junction proteins claudin-1 and occludin, pattern-recognizing receptors, adaptor molecules and coreceptors (RAGE, TLR2, TLR4, TLR9, MyD88, TRIF, MD2, and CD14), and inflammasome NLRP3 transcription were all evaluated. The production of inflammatory mediators IFN-α, IL-4, IL-6, IL-8, IL-10, IL-12/23 p40, TNF-α, IFN-γ, and high mobility group box 1 (HMGB1) in the intestine of germ-free piglets was also assessed. In the preterm germ-free piglets, the ileum showed decreased lamina propria cellularity, reduced villous height, and thinner and less distinct stratification – especially muscle layer, in comparison with their term counterparts. Claudin-1 transcription increased in the intestine of the preterm piglets. The transcription levels of pattern-recognizing receptors and adaptor molecules showed ambiguous trends between the groups. The levels of IL-6, IL-8, IL-10, and TNF-α were increased in the preterm ileum numerically (though not significantly), with statistically significant increases in the colon. Additionally, IL-12/23 p40 and IFN-γ were statistically significantly higher in the preterm colon. Both blood plasma and intestinal HMGB1 levels were nonsignificantly higher in the preterm group. We propose that the intestine of the preterm germ-free piglets showed “mild inflammation in sterile conditions.” This model, which establishes preterm, hysterectomy-derived germ-free piglets, without protective maternal immunoglobulins, can be used to study influences of microbiota, nutrition, and therapeutic interventions on the development and health of vulnerable immunocompromised preterm infants. Frontiers Media S.A. 2018-02-14 /pmc/articles/PMC5817058/ /pubmed/29491864 http://dx.doi.org/10.3389/fimmu.2018.00220 Text en Copyright © 2018 Splichalova, Slavikova, Splichalova and Splichal. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Splichalova, Alla
Slavikova, Vera
Splichalova, Zdislava
Splichal, Igor
Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title_full Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title_fullStr Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title_full_unstemmed Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title_short Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets
title_sort preterm life in sterile conditions: a study on preterm, germ-free piglets
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817058/
https://www.ncbi.nlm.nih.gov/pubmed/29491864
http://dx.doi.org/10.3389/fimmu.2018.00220
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