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 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-gamma), cytokine than mice receiving HAMLET or PBS. IL-17A/IFN-gamma 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.

Automated summary

This study investigated the impact of amoxicillin and HAMLET (human alpha-lactalbumin made lethal to tumor cells) treatment on T cell responses to Streptococcus pneumoniae in infant mice. Lung cells and splenocytes were isolated from mice treated with amoxicillin, HAMLET, or a combination of both, and cultured with S. pneumoniae to measure T cell responses. Results showed that amoxicillin treatment resulted in lower levels of Th17 (IL-17A), but not Th1 (IFN-gamma), cytokine production in lung cells compared to HAMLET or control treatment. However, there were no significant differences in cytokine levels among treatment groups in splenocytes. Flow cytometry analysis revealed decreased levels of IL-17A in lung CD4+, but not CD8+, T cells from amoxicillin- or HAMLET plus amoxicillin-treated mice compared to HAMLET-exposed or control mice. Overall, these findings suggest that amoxicillin exposure may suppress lung Th17 responses to S. pneumoniae in infant mice.