147 The interaction between growth and immunity: Insights into the immune response of finisher pigs with divergent feed efficiency

Abstract

Abstract This work evaluated the immune response of finisher pigs with divergent feed efficiency to identify immune pathways that were associated with efficiency. Blood gene expression data from a previous trial (Liu et al., 2019) were re-analyzed with novel methods that quantified changes in biological pathways and associated them with animal performance. Data were quality control checked and aligned to the Sus scrofa reference genome (Sscrofa11.1) using Kallisto. The dataset had 32 samples from eight pigs with high efficiency (HE) or low efficiency (LE) that had been injected with lipopolysaccharide (LPS). Blood samples were taken before challenge, and at 2, 6, and 24 h after challenge. After normalization and evaluation of differential gene expression, activation or inhibition of pathways was quantified using a topology-based pathway activation method and a customization of the Reactome database. Pathways were associated with feed efficiency using a regularized regression algorithm to identify immune pathways that were associated with efficiency. For statistical analysis, RNA integrity number, feed efficiency and time post LPS challenge were included in the model. At 2 h post LPS, HE pigs showed greater activation in pathways related to heat stress and creatine metabolism, but inhibition of pathways related to lysine and threonine catabolism, and immune resolving mediators (P-adj < 0.01), compared with the response in LE pigs. At 6 h post challenge there was a striking difference in cell cycle response, whereby cell cycle was activated in HE pigs but inhibited in LE pigs (P-adj < 0.01). The biggest difference in immune response was at 24h, with a strong response to LPS still evident in HE pigs, but a diminishing response in LE pigs. High efficiency pigs had activation in pathways related to oxidative stress, the metabolism of tryptophan, serine, tyrosine, threonine, glycogen, vitamin B5, and fibrin clot formation (P-adj < 0.01), which were not evident in LE pigs. The regression of pathways with feed efficiency showed that vitamin B5 metabolism was positively associated with gain:feed, whilst calcium-dependent signaling was negatively associated with gain:feed at multiple timepoints post-challenge. High efficiency pigs appeared to expand leukocyte populations at 6 h post LPS challenge, which was not evident in LE pigs. By 24 h, the response of LE pigs to LPS was minimal, but HE pigs still showed a strong response with greater utilization of energy, amino acids, and more oxidative stress. Low efficiency pigs appeared to recover faster from the LPS challenge, which was partially explained by differences in vitamin B5 utilization and calcium homeostasis. These findings confirm differences in the immune response of HE and LE pigs and provide insights related to amino acid, vitamin B5, and calcium homeostasis, which could help optimize the immune response of HE pigs. The novel analysis methods provided additional insights, which complement the original findings (T1).