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

Shekhar, Sudhanshu ; Brar, Navdeep Kaur LU ; Håkansson, Anders P LU orcid and Petersen, Fernanda Cristina (2023) In Antibiotics 12(2).
Abstract

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
Streptococcus pneumoniae. 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
S. pneumoniae to measure T cell responses. After
in-vitro stimulation with
S.
pneumoniae, lung cells from amoxicillin- or amoxicillin plus HAMLET-treated mice produced lower... (More)

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
Streptococcus pneumoniae. 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
S. pneumoniae to measure T cell responses. After
in-vitro stimulation with
S.
pneumoniae, 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
S. pneumoniae.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amoxicillin, HAMLET, infants, lungs, Th17 immunity
in
Antibiotics
volume
12
issue
2
article number
423
pages
11 pages
publisher
MDPI AG
external identifiers
  • pmid:36830333
  • scopus:85148866895
ISSN
2079-6382
DOI
10.3390/antibiotics12020423
language
English
LU publication?
yes
id
220ee516-5521-4263-b911-51ab14ad9518
date added to LUP
2023-03-03 11:34:06
date last changed
2024-07-12 02:49:39
@article{220ee516-5521-4263-b911-51ab14ad9518,
  abstract     = {{<p>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 <br>
 Streptococcus pneumoniae. 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 <br>
 S. pneumoniae to measure T cell responses. After <br>
 in-vitro stimulation with <br>
 S. <br>
 pneumoniae, 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<br>
 S. pneumoniae.<br>
 </p>}},
  author       = {{Shekhar, Sudhanshu and Brar, Navdeep Kaur and Håkansson, Anders P and Petersen, Fernanda Cristina}},
  issn         = {{2079-6382}},
  keywords     = {{amoxicillin; HAMLET; infants; lungs; Th17 immunity}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  publisher    = {{MDPI AG}},
  series       = {{Antibiotics}},
  title        = {{Treatment of Mouse Infants with Amoxicillin, but Not the Human Milk-Derived Antimicrobial HAMLET, Impairs Lung Th17 Responses}},
  url          = {{http://dx.doi.org/10.3390/antibiotics12020423}},
  doi          = {{10.3390/antibiotics12020423}},
  volume       = {{12}},
  year         = {{2023}},
}