These authors contributed equally to the work.
Direct experimental evidence that early-life farm environment influences regulation of immune responses
Article first published online: 2 FEB 2012
© 2012 John Wiley & Sons A/S
Pediatric Allergy and Immunology
Volume 23, Issue 3, pages 265–269, May 2012
How to Cite
Lewis, M. C., Inman, C. F., Patel, D., Schmidt, B., Mulder, I., Miller, B., Gill, B. P., Pluske, J., Kelly, D., Stokes, C. R. and Bailey, M. (2012), Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatric Allergy and Immunology, 23: 265–269. doi: 10.1111/j.1399-3038.2011.01258.x
- Issue published online: 17 APR 2012
- Article first published online: 2 FEB 2012
- Accepted 18 November 2011
- early life;
To cite this article: Lewis MC, Inman CF, Patel D, Schmidt B, Mulder I, Miller B, Gill BP, Pluske J, Kelly D, Stokes CR, Bailey M. Direct experimental evidence that early-life farm environment influences regulation of immune responses. Pediatr Allergy Immunol 2012: 23: 265–269.
Background: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment.
Methods: Piglets were nursed by their mother on a commercial farm, while isolator-reared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA.
Results: There was more CD4+ and CD4+CD25+ effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4+CD25+Foxp3+ regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets.
Conclusion: Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.