Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses

Emerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor c...

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Main Authors: Sudhanshu Shekhar, Navdeep Kaur Brar, Anders P. Håkansson, Fernanda Cristina Petersen
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/2/423
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author Sudhanshu Shekhar
Navdeep Kaur Brar
Anders P. Håkansson
Fernanda Cristina Petersen
author_facet Sudhanshu Shekhar
Navdeep Kaur Brar
Anders P. Håkansson
Fernanda Cristina Petersen
author_sort Sudhanshu Shekhar
collection DOAJ
description Emerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor cells) on T cell responses to <i>Streptococcus pneumoniae</i>. Lung cells and splenocytes were isolated from the infant mice subjected to intranasal administration of amoxicillin, HAMLET, or a combination of HAMLET and amoxicillin, and cultured with <i>S. pneumoniae</i> to measure T cell responses. After <i>in-vitro</i> stimulation with <i>S</i>. <i>pneumoniae</i>, lung cells from amoxicillin- or amoxicillin plus HAMLET-treated mice produced lower levels of Th17 (IL-17A), but not Th1 (IFN-γ), cytokine than mice receiving HAMLET or PBS. IL-17A/IFN-γ cytokine levels produced by the stimulated splenocytes, on the other hand, revealed no significant difference among treatment groups. Further analysis of T cell cytokine profiles by flow cytometry showed that lung CD4+, but not CD8+, T cells from amoxicillin- or HAMLET plus amoxicillin-treated mice expressed decreased levels of IL-17A compared to those from HAMLET-exposed or control mice. Collectively, these results indicate that exposure of infant mice to amoxicillin, but not HAMLET, may suppress lung Th17 responses to <i>S. pneumoniae</i>.
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spelling doaj.art-335641e4630948ce8793db86906be6eb2023-11-16T18:44:54ZengMDPI AGAntibiotics2079-63822023-02-0112242310.3390/antibiotics12020423Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 ResponsesSudhanshu Shekhar0Navdeep Kaur Brar1Anders P. Håkansson2Fernanda Cristina Petersen3Institute of Oral Biology, University of Oslo, 0316 Oslo, NorwayInstitute of Oral Biology, University of Oslo, 0316 Oslo, NorwayDivision of Experimental Infection Medicine, Department of Translational Medicine, Lund University, 21428 Malmö, SwedenInstitute of Oral Biology, University of Oslo, 0316 Oslo, NorwayEmerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor cells) on T cell responses to <i>Streptococcus pneumoniae</i>. Lung cells and splenocytes were isolated from the infant mice subjected to intranasal administration of amoxicillin, HAMLET, or a combination of HAMLET and amoxicillin, and cultured with <i>S. pneumoniae</i> to measure T cell responses. After <i>in-vitro</i> stimulation with <i>S</i>. <i>pneumoniae</i>, lung cells from amoxicillin- or amoxicillin plus HAMLET-treated mice produced lower levels of Th17 (IL-17A), but not Th1 (IFN-γ), cytokine than mice receiving HAMLET or PBS. IL-17A/IFN-γ cytokine levels produced by the stimulated splenocytes, on the other hand, revealed no significant difference among treatment groups. Further analysis of T cell cytokine profiles by flow cytometry showed that lung CD4+, but not CD8+, T cells from amoxicillin- or HAMLET plus amoxicillin-treated mice expressed decreased levels of IL-17A compared to those from HAMLET-exposed or control mice. Collectively, these results indicate that exposure of infant mice to amoxicillin, but not HAMLET, may suppress lung Th17 responses to <i>S. pneumoniae</i>.https://www.mdpi.com/2079-6382/12/2/423amoxicillinHAMLETinfantslungsTh17 immunity
spellingShingle Sudhanshu Shekhar
Navdeep Kaur Brar
Anders P. Håkansson
Fernanda Cristina Petersen
Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
Antibiotics
amoxicillin
HAMLET
infants
lungs
Th17 immunity
title Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
title_full Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
title_fullStr Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
title_full_unstemmed Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
title_short Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses
title_sort treatment of mouse infants with amoxicillin but not the human milk derived antimicrobial hamlet impairs lung th17 responses
topic amoxicillin
HAMLET
infants
lungs
Th17 immunity
url https://www.mdpi.com/2079-6382/12/2/423
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