Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploite...

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Main Authors: Samanta Mecocci, Livia De Paolis, Roberto Zoccola, Floriana Fruscione, Chiara Grazia De Ciucis, Elisabetta Chiaradia, Valentina Moccia, Alessia Tognoloni, Luisa Pascucci, Simona Zoppi, Valentina Zappulli, Giovanni Chillemi, Maria Goria, Katia Cappelli, Elisabetta Razzuoli
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/12/3264
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author Samanta Mecocci
Livia De Paolis
Roberto Zoccola
Floriana Fruscione
Chiara Grazia De Ciucis
Elisabetta Chiaradia
Valentina Moccia
Alessia Tognoloni
Luisa Pascucci
Simona Zoppi
Valentina Zappulli
Giovanni Chillemi
Maria Goria
Katia Cappelli
Elisabetta Razzuoli
author_facet Samanta Mecocci
Livia De Paolis
Roberto Zoccola
Floriana Fruscione
Chiara Grazia De Ciucis
Elisabetta Chiaradia
Valentina Moccia
Alessia Tognoloni
Luisa Pascucci
Simona Zoppi
Valentina Zappulli
Giovanni Chillemi
Maria Goria
Katia Cappelli
Elisabetta Razzuoli
author_sort Samanta Mecocci
collection DOAJ
description Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by <i>Escherichia coli</i> infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of <i>CXCL8</i>, <i>DEFB1</i>, <i>DEFB4A</i>, <i>TLR4</i>, <i>TLR5</i>, <i>NFKB1</i>, <i>MYD88</i>, <i>CGAS</i>, <i>RIGI</i> and <i>STING</i> were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (<i>p</i> = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in <i>TLR5</i> (<i>p</i> < 0.05), <i>CGAS</i> (<i>p</i> < 0.05) and <i>STING</i> (<i>p</i> < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool.
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spelling doaj.art-1bce35d6e2484b69a14e2bf8016ddc332023-11-24T13:29:41ZengMDPI AGBiomedicines2227-90592022-12-011012326410.3390/biomedicines10123264Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro ModelSamanta Mecocci0Livia De Paolis1Roberto Zoccola2Floriana Fruscione3Chiara Grazia De Ciucis4Elisabetta Chiaradia5Valentina Moccia6Alessia Tognoloni7Luisa Pascucci8Simona Zoppi9Valentina Zappulli10Giovanni Chillemi11Maria Goria12Katia Cappelli13Elisabetta Razzuoli14Department of Veterinary Medicine, University of Perugia, 06123 Perugia, ItalyNational Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Piazza Borgo Pila 39-24, 16129 Genova, ItalyS.C. Biotecnologie Applicate alle Produzioni, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, via Bologna 148, 10154 Torino, ItalyNational Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Piazza Borgo Pila 39-24, 16129 Genova, ItalyNational Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Piazza Borgo Pila 39-24, 16129 Genova, ItalyDepartment of Veterinary Medicine, University of Perugia, 06123 Perugia, ItalyDepartment of Comparative Biomedicine and Food Science, University of Padova, 35020 Legnaro, ItalyDepartment of Veterinary Medicine, University of Perugia, 06123 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, 06123 Perugia, ItalyS.C. Diagnostica Generale, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, via Bologna 148, 10154 Torino, ItalyDepartment of Comparative Biomedicine and Food Science, University of Padova, 35020 Legnaro, ItalyDepartment for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), University of Tuscia, 01100 Viterbo, ItalyS.C. Biotecnologie Applicate alle Produzioni, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, via Bologna 148, 10154 Torino, ItalyDepartment of Veterinary Medicine, University of Perugia, 06123 Perugia, ItalyNational Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Piazza Borgo Pila 39-24, 16129 Genova, ItalyExtracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by <i>Escherichia coli</i> infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of <i>CXCL8</i>, <i>DEFB1</i>, <i>DEFB4A</i>, <i>TLR4</i>, <i>TLR5</i>, <i>NFKB1</i>, <i>MYD88</i>, <i>CGAS</i>, <i>RIGI</i> and <i>STING</i> were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (<i>p</i> = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in <i>TLR5</i> (<i>p</i> < 0.05), <i>CGAS</i> (<i>p</i> < 0.05) and <i>STING</i> (<i>p</i> < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool.https://www.mdpi.com/2227-9059/10/12/3264colostrumExtracellular VesiclescolibacillosiscoloEVsantimicrobial
spellingShingle Samanta Mecocci
Livia De Paolis
Roberto Zoccola
Floriana Fruscione
Chiara Grazia De Ciucis
Elisabetta Chiaradia
Valentina Moccia
Alessia Tognoloni
Luisa Pascucci
Simona Zoppi
Valentina Zappulli
Giovanni Chillemi
Maria Goria
Katia Cappelli
Elisabetta Razzuoli
Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
Biomedicines
colostrum
Extracellular Vesicles
colibacillosis
coloEVs
antimicrobial
title Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
title_full Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
title_fullStr Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
title_full_unstemmed Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
title_short Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model
title_sort antimicrobial and immunomodulatory potential of cow colostrum extracellular vesicles colosevs in an intestinal in vitro model
topic colostrum
Extracellular Vesicles
colibacillosis
coloEVs
antimicrobial
url https://www.mdpi.com/2227-9059/10/12/3264
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