Direct experimental evidence that early-life farm environment influences regulation of immune responses.
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.


CONCLUSIONS
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.
Infection and Immunity, School of Veterinary Science, University of Bristol, Langford, Somerset, UK. marie.lewis@bristol.ac.uk
Marie C
MC
Lewis
Charlotte F
CF
Inman
Dilip
D
Patel
Bettina
B
Schmidt
Imke
I
Mulder
Bevis
B
Miller
Bhupinder P
BP
Gill
John
J
Pluske
Denise
D
Kelly
Christopher R
CR
Stokes
Michael
M
Bailey
D000383:Agriculture; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007107:Immune System; D018928:Immunity, Mucosal; D023421:Models, Animal; D013552:Swine / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014886:Weaning