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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Bibliographic Details
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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Summary: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>.
ISSN:2079-6382