Neonatal Infectious Diseases/Immunology
Neonatal Infectious Diseases/Immunology 3
Mariana R. Brewer, MD (she/her/hers)
Cohen Children's Medical Center
New Hyde Park, New York, United States
Broad-spectrum enteral antibiotics (1gm/L of vancomycin, gentamicin, metronidazole, ampicillin in 2% sucrose) or vehicle (2% sucrose) were administered to 5-wk and 9-wk-old C57BL/6 mice for three continuous wks (n=5 in each group). Following treatment, at 8-wks and 12-wks, mice were euthanized, and spleens were harvested for flow cytometry to examine T cell subsets. Statistical significance (p< 0.05) was determined using 2-way ANOVA with Sidak’s correction for multiple comparisons.
Results: After induction of dysbiosis, all mice developed megacolon. At 8-wks old, dysbiotic mice had a lower absolute number of splenic T cells. Antibiotic-exposed mice also had lower numbers of total CD4 T cells and CD4 memory, naïve, and terminal effector T cell subsets. Although the absolute number of CD8 T cells was not affected by dysbiosis in either age group, 8-wk-old dysbiotic mice had a lower proportion of effector memory CD8 T cells than their unexposed counterparts. In contrast, the absolute number and proportion of regulatory T cells (FoxP3+ CD4+) was higher in 8-wk-old antibiotic exposed mice. Dysbiosis did not affect T cell total or subset numbers in 12-wk-old mice, but it did influence T cell activation. Specifically, antibiotic-exposed 12-wk-old mice had a higher proportion of CD69-positive memory, total CD4, and memory CD4 T cells compared to unexposed mice. Differences in CD69 expression were not noted in 8-wk-old mice.
Conclusion(s): Dysbiosis affects the T cell repertoire differently in young mice compared to older mice. Dysbiosis induction at 5 wks of age led to significant differences in the absolute numbers of various T cell subsets, which were not noted when dysbiosis was induced at 9 wks of age. In contrast, dysbiosis at 12 wks showed differences in the state of activation of CD4 T cells, specifically within the memory CD4 T cell subset. These results show that antibiotic exposure and the resultant dysbiosis, affect T cells differently based on age and could result in a differential effect on immune function.