Oyesola, Oyebola; Alexander E. Downie; Nina Howard; Ramya S. Barre; Kasalina Kiwanuka; Kimberly Zaldana; Ying-Han Chen; Arthur Menezes; Soo Ching Lee; Joseph Devlin; Octavio Mondragon-Palomino; Camila Oliveira Silva; Christin Herrmann; Sergei B. Koralov; Ken Cadwell; Andrea Graham and P’ng Loke
The relative and synergistic contributions of genetics and environment to interindividual immune response variation remain unclear, despite implications in evolutionary biology and medicine. Here we quantify interactive effects of genotype and environment on immune traits by investigating C57BL/6, 129S1 and PWK/PhJ inbred mice, rewilded in an outdoor enclosure and infected with the parasite Trichuris muris. Whereas cellular composition was shaped by interactions between genotype and environment, cytokine response heterogeneity including IFN gamma concentrations was primarily driven by genotype with consequence on worm burden. In addition, we show that other traits, such as expression of CD44, were explained mostly by genetics on T cells, whereas expression of CD44 on B cells was explained more by environment across all strains. Notably, genetic differences under laboratory conditions were decreased following rewilding. These results indicate that nonheritable influences interact with genetic factors to shape immune variation and parasite burden. Oyesola and colleagues show that rewilding mice reveals how genotype and environment combine to determine interindividual immune variation.